Home
Clinical
Research
Education
Grand Rounds
Faculty

Informatics
Links

 

 

 

    QUEST - Anxiety Disorders

Author:
Edward McGonigle, MD

IS GAMMA-KNIFE SURGERY (RADIOSURGERY) EFFECTIVE TREATMENT FOR REFRACTORY OCD?

Best Available Evidence: Lippitz, B.E, Mindus, P., et al. Lesion Topography and Outcome After Thermocapsulotomy or Gamma-Knife Capsulotomy for Obsessive-Compulsive Disorder: Relevance of the Right Hemisphere. Neurosurgery, 44(3): 452-58, March '99.

Design: Retrospective case review

Subjects: 35 Consecutive patients receiving bilateral Thermocapsulotomy(TC) or Gamma-Knife Capsulotomy(GC) for intractable (minimum duration of illness 5 years, all non-surgical treatment options exhausted systematically) at Karolinska Hospital, Stockholm, Sweden between 1976 and 1989.

Outcome Measures: Pre- and post- YBOCS and Comprehensive Psychopathological Rating Scale-OCD subscale and long-term postoperative MRI lesion location

Data: In 29 subjects for which above outcome measures were available (TC n=19, 7 male and 12 female; GC n=10, 5 male and 5 female; median age 40 years; all but one right-handed). Median duration of MRI follow-up 8.4 years

  1. Good outcome (50-100% improvement in rating scales): 9 of 19 in TC group, 7 of 10 in GC group - common denominator in ALL cases was lesion in MIDDLE portion of ant. Limb on RIGHT
  2. Intermediate outcome (5-49% improvement): 5 of 19 in TC group, 1 of 10 in GC group - in 4 of 6 only PART of middle ant. limb compromised*
  3. Poor outcome (<5% improvement): 5 of 19 in TC group, 2 of 10 in GC group - most lesions by MRI located in ANTERIOR portion of ant. limb, one in posterior portion
*In other 2 cases right-sided lesions appeared identical to those in the good outcome group

Limitations: 6 patients unaccounted for, not blinded, not prospective (underway by primary author), detailed psychiatric outcome and patient demographic characteristics not available (in progress), morbidity and mortality not included

Strengths: Same MRI scanner and protocol used for all patients, single surgical group performing procedure

Clinical Bottom Line: Best evidence supports targeting middle portion of anterior limb of right internal capsule with gamma-knife radiosurgery technique may be an effective treatment for patients with significant debilitation following psychopharmacologic and psychotherapeutic treatment of Obsessive-Compulsive Disorder

Return to top of the page

VENLAFAXINE ER AS A TREATMENT FOR GAD IN OLDER ADULTS

Bottom Line: Venlafaxine ER is equally safe and well tolerated by and shows similar efficacy in young and older patients in the treatment of GAD.

Background: Although GAD is a common psychiatric disorder in older adults, it is often under diagnosed and under treated. Estimates of 6 month prevalence in older (age>=60) community dwelling patients has recently been estimated as high as 17.3% in the U.S. Treatment for GAD in older adults often consists of low dose bzd, despite concerns that these are associated with memory loss, psychomotor impairment, auto accidents and falls. There is also concern re: abuse or dependency with chronic use. Venlafaxine is an alternative with good tolerability profiles and no dependence, tolerance or amnesitic effects.

Clinical Question: Evaluate utility of Venlafaxine ERTM specifically in older patients with a diagnosis of GAD. a

Reference: Katz, Ira R, MD, PhD et al, "Venlafaxine ER as a Treatment for Generalized Anxiety Disorder in Older Adults: Pooled Analysis of Five Randomized Placebo-Controlled Clinical Trials", Journal of American Geriatric Society, V. 50, January, 2002, pp. 18-25.

Methods: Authors conducted a series of post hoc analyses comparing efficacy and safety of Venlafaxine ER vs placebo in sub samples of older and younger patients using pooled data from 5 separate manufacturer-initiated studies. These were all prospective, double-blind, randomized, placebo-controlled clinical trials. There was no apparent screening for studies, just pre selection of these 5. Subjects were outpatients, 18 or older, with a diagnosis of GAD per DSM-IV and a HAM -A score of >=18 with at least moderate symptoms of anxious mood and tension (scores >=2 for items 1 &2). Exclusion criteria: Diagnosis of MDD w/in 6 months of tudy entry; depressive symptoms (per Rankin Scale) greater than anxiety symptoms (per Covi Scale); any diagnosis of primary psychosis or BPAD; previous use of venlafaxine ER; drug allergy, clinically significant medical illness that might compromise the study, MI w/in 6 months; substance dependence within 1 year; > lg caffeine per day or clinically significant abnormalities on physical exam or lab tests. Primary Outcomes: HAM -A total score (Response = 50%. in HAMA, Remission = <7 HAMA); psychic anxiety factor; anxiety subscale of Hospital Anxiety & Depression Scale and CGI Impression of Improvement (Response =1 or 2). Secondary Outcomes: HAMA somatic anxiety factor, HAD depression subscale, CGI severity, Covi Scale for Anxiety ad Raskin Scale for Depression. Primary efficacy evaluations were based on intention-to-treat analyses. Analyses of continuous measures such as efficacy rating scales were conducted using three way analysis of covariance with treatment, study, age group and treatment by age group interaction in the model and baseline as a covariate. The percentages of responders and remitters and incidence of study events and reasons for termination were analyzed using logistic regression with treatment, study, age group and treatment by age group interaction in the model.

Results:
As for efficacy outcomes, owing to limited statistical power for detection of decrements in venlafaxine ER placebo differences between younger and older sub samples, the authors felt guided to perform evaluation of effects of the drug with a series of post hoc analyses within each of the two age-defined subgroups of patients (young < 60yo; older >= 60yo). During first 8 weeks, significant drug-placebo differences were noted in older patients in LOU on HAMA psychic anxiety factor and HAD anxiety subscale. In 24 week analyses, drug-placebo differences were noted in HAMA anxiety factor and CGI in both LOCF and observed-case analyses. However, in both time periods, the difference between placebo and drug impact on primary and secondary measures is small, and in general less than one-half the size of the placebo effect.

As for analyses of responses, tests at Week 8 found significant drug-placebo differences for older adult patients in the LOCF analyses of responders on the CGI-I and both responders and remitters on the HAM A. In the 24 week analyses of the older subgroup, there was a significantly higher rate of responders to venlafaxine ER than to placebo on both the HAMA and CGI-I scales. However, the CGI-I is not specific as an objective measure of patient's anxiety symptoms (the focus here) and the "n" for the 24 week results is quite low for the "Older" group.

A review of rate of treatment-emergent adverse events demonstrated a main effect for age, with inverse relationship. Among categories of adverse events leading to discontinuation, there were main effects of treatment in events related to digestive and metabolic systems, but no age effects or age by treatment interactions. Percent of participants discontinuing due to lack of efficacy was significantly different, favoring venlafaxine, only in the younger group.

Conclusions:
Though the current does study shows that venlafaxine produced improvement (as measured across multiple scales) statistically greater than that seen with placebo in elderly (age >60), it does suffer from some weaknesses.  In looking to combine multiple pat studies the authors did not screen all past studies comparing venlavaxine vs placebo, but arbitrarily chose 5 manufactures initiated studies.  Exclusion criteria were vague (physical or laboratory abnormalities) or excluded many who may by that same criteria may have significant anxiety (MI w/in 6 months); and also created a selection bias in that those - had been tried on venlafaxine (and who by being in this study must have GAD and HAMA > 18) who would be known non-responders, were excluded. Moreover, though there is statistical significance to the difference of primary measures for drug and placebo, the meaning of such small differences in terms of improvement of functioning is vague.
Perhaps more rigorous results could come from screening literature for all studies which by similarity of design would allow pooling of results, allowing for greater N, hence greater power. Moreover, allowing the medical exclusion criteria to be only a strict contraindication to the use of venlafaxine XR would provide for greater validity.

Return to top of the page

Author:
Sandeep Vaishnavi, MD, PhD

IS LIGHT THERAPY AN EFFECTIVE TREATMENT FOR SAD?

Reference: Eastman, Young, et. al. Bright Light Treatment of Winter Depression, Arch Gen Psychiatry, 1998 (55, 883-889)

Bottom line: Light therapy is a better antidepressant for SAD than placebo, but not until the 3•' week of treatment and only when comparing percent of full remissions

Methods/Results Validity
Design - RCT with 3 arms: morning light (6 AM), evening light (9 PM), and morning placebo (6 AM). Treatment consisted of 6000 lux lights; placebo was a sham negative ion generator; tx was for 6 days/week for 4 weeks
Patient Population - 121 pts randomized into 3 arms (but balanced for gender); 25 dropped out (8 from 2 of the groups and 9 from the third group, leaving 96 pts)
Inclusion criteria -Pts had to meet the diagnostic criteria for SAD in addition to increased appetite/weight and increased sleep criteria; pts had to score 21 or more on the first 24 items of the SIGH-SAD. None of the pts could have tried light therapy or negative ion therapy (the stated placebo), no psychotropic meds for several months
Blinding of those performing and/or undergoing the treatment- Yes, staff giving weekly SIGH-SAD ratings were blind to pts' type of equipment and time of day of treatment. Staff that gave the treatments were not aware which pts had active vs. inactive tx
Randomization - Yes, although it was not mentioned exactly how randomization occurred and how the groups were balanced for gender and number
Were all pts who entered the trial properly accounted for and attributed at the conclusion? No. 25 pts dropped out of treatment, but they were not utilized in the data analysis
Were groups similar at the start of the trial? Yes, with no significant difference between groups in terms of expectations and with groups being similar in age, gender, and education Analysis - Repeated-measures ANOVA, correlation coefficient, log linear analysis Outcomes - 1. There were no statistically significant difference between the 3 groups in terms of expectations for success; there was correlation between expectation and depression ratings (p=0.04 at week 3). 2. ML group had significantly more sleep than the EL group. 3. No significant difference between 3 groups on SIGH-SAD score (p=0.42). 4. When comparing pts with 50% decrease of score from baseline, no significant difference between groups. 5. When comparing pts with a decrease of 50% and a score less then or equal to 8, ML was significantly better than MP at weeks 3 and 4; ML>EL at week 3. 6. When comparing pts who meet the above criteria on weeks 3 and 4, ML > MP and EL (so overall, ML produced the greatest number of full remissions). 7. With Beck Depression scores, ML > MP in percent responders, but no difference between ML and EL.

Comments
Strengths and Weaknesses of Study - strengths: 1. It is a RCT. 2. It has an appropriate placebo control. Weaknesses: 1. Multiple comparisons needed before any significant difference found (which increases chances of Type I statistical error and a significant difference may be found artificially). 2. Randomization unexplained. 3. No EP. 4. Dropouts evidentally not used in data analysis. 5. Inconsistent results when using SIGH-SAD vs. Beck Depression Score
How will this study affect your management?  Evidence for photo therapy for SAD is weaker than often appreciated and one may be less likely to use it for SAD pts
Next steps for further study of this problem - EP, larger pt population to tease out a significant difference, if any

Return to top of the page

SYMPTOM STABILITY IN OCD  

 

Reference: David Mataix-Cols, Ph.D., Scott L. Rauch, M.D., et al. Symptom Stability in Adult Obsessive­Compulsive Disorder: Data From a Naturalistic Two-Year Follow-Up Study, Am J Psychiatry 2002; 159:263-268.

Background: Attempts to address the heterogeneity of OCD has yielded 3-5 OCD dimensions via factor analytic studies. Per the authors, prior studies have suggested a relationship between certain dimensions and socio demographic, genetic, and physiologic variables. If patients remain stable within a dimension, thereby decreasing the heterogeneity of OCD, further information about the neurobiology of OCD can be obtained. However, prior studies have shown that OCD symptoms change over time. This study attempts to answer 1) Are individual symptoms of adult OCD stable across time? 2) Are previously identified symptom dimensions of OCD stable? 3) Are some symptoms more stable than others? 4) Can changes be attributed to the effects of treatment? 5) Do changes occur within symptom dimensions, or, are there shifts from one dimension to another?

Methods:

Design - Naturalistic Prospective Study.

Setting - Three specialized university-based (Brown, Yale, and Harvard [MGH]) OCD clinics

Patient Population - Inclusion criteria were age of 18 years or older and a willingness to be followed for 2 years. The diagnosis of OCD was confirmed in all cases by experienced interviewers through use of a structured diagnostic interview. ( Patients with comorbid diagnoses were not excluded if OCD was the dominant disorder) The study yielded a sample of 117 patients.

Description of OCD symptoms-The 10-item clinician-rated Yale-Brown Obsessive Compulsive Scale and the Yale-Brown Obsessive Compulsive Scale symptom checklist which consist of 50 items which are separated into 13 OCD categories. The patients' scores on the five symptom dimensions were computed by summing the scores of the symptom categories under each dimension; these scores were then used in all subsequent data analyses. The five symptom dimensions were symmetry/ordering, hoarding, contamination/ cleaning, aggressive/checking, and sexual/religious obsessions. Analysis -

A) For each individual Yale-Brown Obsessive Compulsive Scale symptom category, McNemar's tests were used to determine the significance of changes in symptoms.

B) To analyze changes in symptom severity (10-item Yale-Brown Obsessive Compulsive Scale) and within the five previously identified OCD symptom dimensions, comparisons of the current symptoms at baseline and at 6-month, 1-year, and 2-year follow-ups were made. Then they were applied to repeated measures analyses of variance.

C) The percent decrease from baseline to 2-year follow-up on the total Yale-Brown Obsessive Compulsive Scale score was included as a covariate in the analyses to address changes within symptom dimensions confounded by overall reduction in OCD severity attributable to treatment.

D) A series of stepwise multiple regression models were tested in which each symptom dimension at a given follow-up point was the dependent variable and all five OCD symptom dimensions at the immediately preceding follow-up point were entered as independent variables to assess the degree of change between previously identified OCD symptom dimensions, (Significance level was set at p<0.01 to control for possible type I errors due to multiple testing. )

Follow-up -Of the initial group of patients, 81(69%) attended their respective clinics at 6-month follow up, 83 (71%) at 1-year follow-up, and 67 (57%) at 2-year follow-up. There were no statistically significant differences in baseline characteristics between subjects who did or did not participate in the follow-up evaluations. Accounting for dropouts was not addressed.

Validity:

Definition of patient sample-The study didn't address whether the same experienced clinical interviewer interviewed at each site. The study did not address the structured clinical interview used. Variations in demographics were not given only the number of men and women, mean age and scores. There was no information about time since onset of OCD symptoms for the patients.

Is the study representative of clinical practice-NO. The study was performed at specialized OCD clinics at university hospitals

Was duration of follow-up sufficient? Information about treatment was available only from 2 sites where

66 patients had SRI's for 12 weeks or more and 12 patients had had an "adequate" trial of behavior therapy. Were all patients accounted for? NO

Were outcome criteria objective and unbiased relative to the OCD symptoms? NO. The training of the clinician or blinding to treatment was not addressed in the study.

Was their adjustment for linked OCD symptoms? YES. OCD symptoms determined which dimension the patient was placed.

Were patients in the study treated similarly? Unlikely considering some patient's received behavioral therapy and others had medication management.

Results

A) McNemar's tests showed that the symptoms of some patients changed significantly from baseline to 6­month follow-up. When using p<0.01 Changes were more likely to occur in aggressive obsessions, as well as in cleaning, checking, counting, ordering, and hoarding compulsions. When we used a less stringent 0.05 significance level, changes were observed in contamination, hoarding, and symmetry obsessions as well. Only cleaning showed a significant change outside of the first six months. (Table 1)

B) Repeated measures ANOVAs showed significant differences over time on the aggressive/checking (F=9.94, df=3, 150, p 1]0.001), symmetry/ordering (F=6.43, d=3, 150, p= 0.001), and contamination/cleaning (F=4.16, df-3,150, p=0.007) dimensions. The hoarding and sexual/religious dimensions remained mostly unchanged across time (Fig 1).

Repeated measures ANOVAs found significant improvements on the Yale-Brown Obsessive Compulsive Scale total score               from pretreatment (mean=20.7, SD--9.6) to 2-year follow-up (mean=15.8, SD=8.9) (F= 10.66, epsilon-corrected df=1.9, 85.1,   p00.001).

 C) Repeated measures analyses with the percent drop on the total Yale-Brown Obsessive Compulsive Scale over the 2-year                                     period as a_covariate yielded non significant covariance coefficients, suggesting that changes within symptom dimensions of OCD were independent from the overall reduction in symptom severity.

D) Multiple regression analyses showed strong partial correlations between each OCD symptom dimension at a given follow-up point and the same dimension at the immediately previous point, whereas significant correlations between different dimensions were rare and small (Table 2) There were strong partial correlation between each OCD symptom dimension at different follow-up points with respect to baseline scores on the same dimension. Overall, most partial correlation were greater than 0.60 the only exception was the aggressive/checking dimension, which had the smallest partial correlations across time.

Comments

Strengths and Weaknesses of Study- The study did not differentiate the patient's on the basis of the type of treatment they received. Moreover, the frequency and duration of patient contact during this treatment was not addressed. Of note, the information about the patients' treatment was not available given that the MGH did not have the information available. The was question of reliability of diagnosis in using SCII) and whether the clinicians administering the 10 item scale were blinded to the patient's follow up schedule or the type of treatment the patient was receiving. There was no explanation of how the information from the clinicians 10-item scale was incorporated into the study. There was question about accounting for patients in the studied, which appear to have fluctuated at follow-ups.    Demographic similarity of the patient's was not addressed in the study. Analysis of information from drop out was not addressed. There was no indication that the patient's were treated similarly not only between sites but within sites also.

Return to top of the page

Author:
Kerry Landry

OLANZAPINE IN ANXIETY DUE TO ALZHEIMER'S DISEASE

Clinical Question: 76yo MWF with vascular dementia presents complaining of persistent anxiety. What medication will be of any help?

Reference: Mintzer J, Faison W, et al. Olanzapine in the treatment of anxiety symptoms due to Alzheimer's disease: a post hoc analysis. Int J Geriatr Psychiatry, 2001, vol 16: S71-S77.

Background: Alzheimer's disease is associated with both cognitive and behavioral symptoms. Agitation, hallucinations, delusions, aggression, irritability, and anxiety are observed in up to 90% patients with dementia. Although new information has emerged on the treatment of psychosis and agitation in dementia, very little is available about the treatment of anxiety symptoms in this population.

Methods
Design - RCT, double-blind, placebo-controlled 6-week study.
Setting-28 sites in US from 12/1996-6/1998.
Patient Population - Eligible patients were >40yo, nursing home residents with score >=3 on any of the Neuropsychiatric Inventory/Nursing Home (NPI/NH) Agitation/Aggression, Delusions, Hallucinations items & MMSE <25. Exclusion criteria: bedridden, h/o Axis I disorder within 12mos prior to study entry, or any other diagnosis of serious neurological condition other than AD that could contribute to psychosis or dementia. No concomitant use of medications with primarily CNS activity (i.e. cholinesterase inhibitors, anticonvulsants, mood stabilizers, other antipsychotics, TCA's, MAOI's, and anticholinergics). Patients were allowed to continue SSRI's, but could not alter the medication after screening.

This study used a subset of patients who presented with clinically significant anxiety symptoms, defined as score >=2 on NPI/NH Anxiety item. This patient subgroup of 120 subjects (58.3% of entire study population), was mostly female (72%), evenly divided between those up to 85yo and those older than 85yo, and had mean baseline MMSE 7.43.

Intervention / Control - Olanzapine / Placebo. Benzodiazepines were utilized as rescue medication, up to 4mg/d ativan-equivalents and a total of 21 days during treatment period.

Baseline l-'washout and placebo lead-in period (3-14d)-*randomization via permuted block design to 1 of 4 fixed-dose treatment groups (placebo; olanzapine 5, 10, or 15mg/d)-* Weekly evaluations for up to 6 weeks.

Titration: All patients assigned to olanzapine therapy began at 5mg/d, with subsequent increases of 5mg every 7d for those assigned to 10 and 15mg/d groups.

Blinding-"double-blind," with no specifics
Outcomes - Patients were evaluated at baseline & weekly for up to 6 weeks. NPI/NH = caregiver-rated scales that assess psychopathology in dementia.
     Primary: NPI/NH, including items of Delusions, Hallucinations, 
     Agitation/Aggression and Anxiety, and the Brief Psychiatric Rating Scale 
     for efficacy.
     Secondary: Simpson-Angus Scale, AIMS, and Barnes Akathisia Scale, 
     and MMSE for tolerability and safety. Also included adverse events, vitals 
     signs, weight, lab tests, and ECG's.
Follow-up - 6 week period total. 29 of the anxiety subgroup patients discontinued prior to completion, 11 physician's decision, and 3 d/t noncompliance.
Analysis - ITT with LOCF, Mean change from baseline to endpoint was analyzed using ANOVA. Fisher's Exact test was used to analyze categorical data to determine statistical significance.

Validity
Randomized and Randomization list concealed? yes
Treatment groups similar at baseline? yes. 
There were no statistically significant differences across treatment groups in baseline characteristics of this subset. (see table 1) 
Patients starting trial accounted for at conclusion? yes 
Patients     analyzed in groups to which they were randomized? yes 
Patients and clinicians blinded to treatment? yes
Groups treated similarly outside of intervention? yes
Do the study population characteristics describe your patient? no-she likely has vascular dementia.

Results
For efficacy outcomes - Only patients treated with olanzapine 5mg/d had statistically sig reduction on Anxiety item as compared to placebo (olanz 5: -3.72, placebo: -1.67, p"0.034). This finding also held true in full study group. In overall study, low dose olanzapine (5& 10mg/d) was statistically more effective than placebo at reducing psychosis. When controlling for the improvement in hallucinations from baseline to endpoint, the improvement in anxiety in the olanzapine 5mg/d group remained statistically significant. No statistically sig changes in MMSE scores across treatment groups.

For safety and tolerability outcomes - Somnolence was the only treatment-emergent event that was statistically different in any olanzapine group compared with placebo. When controlling for treatment­emergent somnolence, the improvement in anxiety in the olanzapine 5mg/d group remained statistically significant. Also true when controlled for use of BZ's as rescue medication.

Compliance with Therapies - Not clear how compliance was monitored, but 3 patients were dropped due to "noncompliance."
Adverse Effects - Olanzapine was well tolerated, but 11 patients did withdraw from study d/t adverse event (not specified). Ecchymosis more often in placebo group. Somnolence more often in olanzapine groups. No adverse events, EPS, changes in vital signs, lab values, and ECGs occurred with statistical significance.

Comments
Strengths: moderate number of subjects, multicenter
Weaknesses: only anxiety in AD, too many medications on exclusion list, no long-term follow up beyond 6 weeks, no mention what specific adverse events caused patients to drop out 
How will this study affect your management of the putative patient? not at all-she's already been on olanzapine with no benefit
Next steps for further study of this problem: Long term study, broaden subject pool to assess effectiveness in other types of dementia and with other medications used in patients with dementia, improved monitoring/ reporting of AE's.

Return to top of the page

EBM Type: Therapy Article
Clinical Question: Does placebo have differential effect on different psychiatric disorders?
Reference Jonathan D. Huppert, et al. Differential Response to Placebo Among Patients With Social Phobia, Panic Disorder, and Obsessive-Compulsive Disorder. (Am J Psychiatry
 2004; 161:1485-1487)
Methods
Design - Treatment response and patients' treatment expectancy were examined by using data from 70 patients with obsessive-compulsive disorder, social phobia, or panic disorder who received placebo in three randomized, controlled trials comparing cognitive behavior therapy, medication, and their combination to placebo. These data are obtained from independent RCTs at different medical centers.

Patient Population - Patients from multi-center research clinics.

Inclusion criteria and Exclusion criteria: All studies had similar inclusion criteria (e.g., adults with primary OCD, social phobia, or panic disorder) and exclusion criteria (e.g., no psychosis, mania, or substance abuse). However, unlike the other studies, the panic disorder study (10) did not exclude patients with major depression but did exclude moderate to severe agoraphobia.

Screening/enrollment methods:

Intervention / Control: 1) 26 patients with OCD who received placebo in a randomized clinical trial that compared 12 weeks of cognitive behavior therapy, clomipramine, their combination, and placebo (8); 2) 60 patients with social phobia who received placebo in a randomized clinical trial that compared 14 weeks of group cognitive behavior therapy, fluoxetine, their combination, placebo, and cognitive behavior therapy plus placebo (9); and 3) 24 patients with panic disorder who received 12 weeks of placebo in a randomized clinical trial that compared 12 weeks of cognitive behavior therapy, imipramine, their combination, placebo, and cognitive behavior therapy plus placebo (10). Psychopharmacologists saw patients for similar amounts of time in each study, and exposure to anxiety-provoking situations was not systematically encouraged during these visits.

Assessments: All studies included independent raters blind to treatment assignment and used the Clinical Global Impression (CGI) (11) severity and improvement scales, the 17-item Hamilton Depression Rating Scale (12), and a symptom -specific measure: the Yale-Brown Obsessive Compulsive Scale (13) for OCD, the Duke Brief Social Phobia Scale (14) for social phobia, or the Panic Disorder Severity Scale (15) for panic disorder.

 Analysis - non-ITT for presented results but ITT analysis had same results for the between the group comparisons. Effect sizes were calculated for the symptom measures. CGI severity and Hamilton depression scale scores were compared between and within groups by using analyses of variance for pretreatment scores, analyses of covariance for post treatment scores (covarying pretreatment severity), and paired-sample t tests for within-subject change scores. CGI improvement scores were compared by means of chi-square tests of ordinal data. Analyses were conducted separately for the completers and for all randomly assigned patients with any available data by using the last observation carried forward (intent-to-treat group).

VALIDITY
Data used in three randomized, placebo-controlled trial, with blindness in ratings. Treatment groups appear to be similar at baseline but not explicitly expressed. ITT analysis used but not shown.
Completers were analyzed in groups to which they were randomized presented in this paper.
Raters were blinded. Pt may have some level of blindness (real pills vs. placebo).
Groups are from different pt populations. They appear to be treated similarly outside of placebo intervention but not mentioned.
Do the study population characteristics describe your patient? Yes.

Results
The OCD patients receiving placebo had less symptom improvement than the patients with either social phobia or panic disorder in both the completer (Table 1) and intent-to-treat groups. When the most severe cases were excluded (CGI severity score=6) to eliminate significant pre-treatment CGI severity differences between the patient groups (F=2.2, df=2, 56, p=0.12), the patients with OCD continued to show less improvement at post-treatment than those with social phobia or panic disorder (p<0.01, ANCOVA). Ratios of the effect sizes for active medication and exposure therapy to the effect size for placebo were calculated to determine the treatment responsiveness of the groups. All groups showed at least a 40% larger effect size for the active treatments than for placebo, with the OCD patients showing the largest treatment effects, owing to the smallest placebo effects.

CONCLUSIONS:
Patients with obsessive-compulsive disorder were less likely to respond to placebo than patients with generalized social phobia or panic disorder. Differential expectancy did not account for these findings.

Comments
Strengths 
Three RCTs with similar designs, particularly for the placebo group. Comparison across different studies.

Weakness: sample sizes are rather small for each group, subjective to errors. Internal validity can be challenging from comparing different studies with different populations. External validity is unknown (generalized). Non ITT analysis might amplify the results.

Study in context of other available literature and/or current standard-of care: Novel study.

 How will this study affect your management of the putative patient? No effect at this time.

Next steps for further study of this problem- none.

In summary, given these limitations, this study provides an insight into different aspects of different anxiety disorders, which may elucidate mechanisms of these disorders and have implications for treatment.

Return to top of the page