CGI-S) And Improvement Research Articles

The Treatment of Depressed Chinese Americans Using Qigong in a Health Care Setting: A Pilot Study

Background. This pilot study examined the feasibility and efficacy of providing Qigong treatment in a health center to Chinese Americans with major depressive disorder (MDD). Methods. Fourteen Chinese Americans with MDD were enrolled, and they received a 12-week Qigong intervention. The key outcome measurement was the 17-item Hamilton Rating Scale for Depression (HAM-D17); the Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I), the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF), and the Multidimensional Scale of Perceived Social Support (MSPSS) were also administered. Positive response was defined as a decrease of 50% or more on the HAM-D17, and remission was defined as HAM-D17 ≤ 7. Patients' outcome measurements were compared before and after the Qigong intervention. Results. Participants (N = 14) were 64% female, with a mean age of 53 (±14). A 71% of participants completed the intervention. The Qigong intervention resulted in a positive treatment-response rate of 60% and a remission rate of 40% and statistically significant improvement, as measured by the HAM-D17, CGI-S, CGI-I, Q-LES-Q-SF, and the family support subscale of the MSPSS. Conclusions. The Qigong intervention provided at a health care setting for the treatment of primary care patients with MDD is feasible. Further studies with larger sample sizes are warranted.

A Phase 2a Randomized, Parallel Group, Dose-Ranging Study of Molindone in Children with Attention-Deficit/Hyperactivity Disorder and Persistent, Serious Conduct Problems

To evaluate safety and tolerability of four doses of immediate-release molindone hydrochloride in children with attention-deficit/hyperactivity disorder (ADHD) and serious conduct problems. This open-label, parallel-group, dose-ranging, multicenter trial randomized children, aged 6-12 years, with ADHD and persistent, serious conduct problems to receive oral molindone thrice daily for 9-12 weeks in four treatment groups: Group 1-10 mg (5 mg if weight <30 kg), group 2-20 mg (10 mg if <30 kg), group 3-30 mg (15 mg if <30 kg), and group 4-40 mg (20 mg if <30 kg). The primary outcome measure was to evaluate safety and tolerability of molindone in children with ADHD and serious conduct problems. Secondary outcome measures included change in Nisonger Child Behavior Rating Form-Typical Intelligence Quotient (NCBRF-TIQ) Conduct Problem subscale scores, change in Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I) subscale scores from baseline to end point, and Swanson, Nolan, and Pelham rating scale-revised (SNAP-IV) ADHD-related subscale scores. The study randomized 78 children; 55 completed the study. Treatment with molindone was generally well tolerated, with no clinically meaningful changes in laboratory or physical examination findings. The most common treatment-related adverse events (AEs) included somnolence (n=9), weight increase (n=8), akathisia (n=4), sedation (n=4), and abdominal pain (n=4). Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). The incidence of AEs and treatment-related AEs increased with increasing dose. NCBRF-TIQ subscale scores improved in all four treatment groups, with 34%, 34%, 32%, and 55% decreases from baseline in groups 1, 2, 3, and 4, respectively. CGI-S and SNAP-IV scores improved over time in all treatment groups, and CGI-I scores improved to the greatest degree in group 4. Molindone at doses of 5-20 mg/day (children weighing <30 kg) and 20-40 mg (≥ 30 kg) was well tolerated, and preliminary efficacy results suggest that molindone produces dose-related behavioral improvements over 9-12 weeks. Additional double-blind, placebo-controlled trials are needed to further investigate molindone in this pediatric population.

Efficacy of Dose Increase Among Nonresponders to Low-Dose Aripiprazole Augmentation in Patients With Inadequate Response to Antidepressant Treatment:

To examine the efficacy of a dose increase of aripiprazole to 5 mg/d in subjects with major depressive disorder (MDD) who did not respond to 4 weeks of treatment with aripiprazole 2 mg/d in a randomized, double-blind, placebo-controlled, parent study. 221 Subjects with Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition-diagnosed DSM-IV-TR MDD (mean ± SD age, 45 ± 11 years; 64% women) with inadequate antidepressant response were recruited from September 2008-July 2009 and randomized to 60 days of double-blind augmentation with either aripiprazole or placebo in two 30-day phases. The study was performed across 8 academic hospital sites and 14 nonacademic (private clinic) sites throughout the United States. Randomization in a 2:3:3 ratio per sequential parallel comparison design was drug/drug (aripiprazole 2 mg/d in phase 1 and 5 mg/d in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1 and aripiprazole 2 mg/d in phase 2). In phase 2, we examined efficacy of an aripiprazole dose increase to 5 mg/d in nonresponders to 2 mg/d by assessing response rates (≥ 50% reduction in Montgomery-Asberg Depression Rating Scale [MADRS] score [primary outcome measure]) and score changes in MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, 9-item Patient Health Questionnaire (PHQ-9), the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, and patient-rated versions of the CGI-I and CGI-S scales. Response rate for aripiprazole 2 mg/d in phase 1 was 18.5% (n/n = 10/54). Among 39 nonresponders who increased their dose to 5 mg/d, response rate was 12.8% (95% CI, 4.30%-27.43%), with significant overall mean ± SD reductions in MADRS scores (-9.46 ± 7.83 [95% CI, -12.00 to -6.92]; P < .0001), Symptoms Questionnaire Distress scores (19.51 ± 17.73 [95% CI, 13.60 to 25.43]; P < .0001), PHQ-9 scores (-7.92 ± 5.92 [95% CI, -9.89 to -5.94]; P < .0001), and CGI-S scores (-0.86 ± 0.86 [95% CI, -1.15 to -0.58]; P < .0001). Differences in efficacy between drug and placebo groups were nonsignificant, however. Aripiprazole and placebo were well tolerated. Augmentation with aripiprazole 5 mg/d may provide only a modest additional benefit in patients who do not benefit from lower doses. clinicaltrials.gov Identifier: NCT00683852.

Aripiprazole augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a 10-week open-label study

Studies investigating the aripiprazole augmentation treatment of serotonin reuptake inhibitor (SRI)-resistant obsessive-compulsive disorder (OCD) are insufficient. The aim of the present pilot study was to investigate the efficacy and tolerability of flexible doses of aripiprazole as an augmenting agent in SRI-resistant OCD patients. OCD patients who met the criteria of this study were followed up with flexible doses of aripiprazole augmentation over a 10-week period. Effectiveness of treatment was evaluated via the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. At the end of the 10-week follow-up period, patients who showed an improvement of ≥30% for the Y-BOCS total score from baseline were considered responders. Thirty patients met the study inclusion criteria; three patients did not agree to participate, and four patients dropped out of the study. The differences between baseline and scores at 10 weeks for the parameters studied were as follows: Y-BOCS scores: 32.0±6.3-24.0±8.1 (Z=4.2, P<0.05); Y-BOCS compulsion subscore: 15.0±4.2-11.5±4.3 (Z=4.01, P<0.05); Y-BOCS obsession subscore: 17.0±2.6-12.4±4.0 (Z=4.1, P<0.05); and CGI-S scores: 4.8±0.8-3.1±1.2 (Z=3.9, P<0.05). Patients showed a significant improvement over the 10-week study period; however, only seven of 23 patients (30.4%) who completed the study met the criteria determined for treatment response. Despite the limited number of cases and open-label design of this study, results support the notion that adding aripiprazole to SRIs could be a valid strategy for treatment-resistant OCD patients.

Long-term, Open-label Study of Once-daily Ropinirole Prolonged Release in Early Parkinson's Disease

ABSTRACTLong-term safety and efficacy of once-daily ropinirole prolonged release (PR) were evaluated in subjects with early Parkinson's disease (PD). Subjects (n = 83) who completed one of two studies were enrolled in this open-label, multicenter, extension study, and followed for up to 78 months. Ropinirole PR was titrated/continued, and adjusted as appropriate during the maintenance phase (maximum 24 mg/day). L-dopa and other non-dopamine agonist PD medications were permitted. Safety outcomes included adverse events (AEs). Efficacy outcomes included Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores, and Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I) scores. The median duration of ropinirole PR exposure was 1,069 days. Most subjects (97.6%) reported at least one AE, most commonly (≥30%) nausea (42.2%), dizziness (41.0%), peripheral edema (38.6%), back pain (33.7%), and headache (31.3%). Seventeen (20.5%) subjects discontinued due to an AE. UPDRS and CGI scores indicated that the clinical status of subjects was maintained throughout the treatment period. In patients with early PD, long-term treatment with once-daily ropinirole PR was not associated with any new safety concerns, and was effective in maintaining clinical status. These results support the extended use of ropinirole PR for treatment of PD.

Depression in hospitalized patients with malignant melanoma treated with interferon-alpha-2b: primary to induced disorders

Our objective was to study the clinical and management differences between primary and interferon (IFN)-induced depressive disorders in malignant melanoma patients visited by the consultation-liaison team during a two year period. This was a prospective study of 31 patients with malignant melanoma treated with IFN-alpha in a general teaching hospital. Clinical, psychiatric variables and DSM-IV-TR diagnosis were analyzed. The Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) of illness scales were administered at the time of consultation and at the end of hospitalization. The main diagnoses were depressive adjustment disorders in 14 patients (45.16%) followed by interferon-induced depressive disorders in 6 (19.36%). In patients with adjustment disorders, melanoma stage was significantly more advanced than in those with interferon-induced depressive disorder (p = 0.019). The latter scored higher in the CGI-S scale (p = 0.044) and in the CGI-I scale (p = 0.029). The interferon-induced depressive disorders, except one who required a reduction of IFN-alpha-2b dose, were successfully treated with antidepressant drugs. Clinical management and antidepressant treatment allowed the continuation of interferon therapy in malignant melanoma patients. Interferon-induced depression occurred in a few patients, which in turn were the most severe. Adjustment depressive disorder was the most common psychiatric diagnosis.

Treatment of Clozapine-Induced Hypersalivation With Ipratropium Bromide

Clozapine-induced hypersalivation (CIH) occurs in up to 57% of treated patients and can be the source of considerable subjective distress. Previous open-label studies suggest that sublingual ipratropium bromide may be effective in treating CIH. We conducted a randomized, double-blind, placebo-controlled crossover trial to evaluate the efficacy of ipratropium in 20 individuals with CIH between September 2006 and August 2007. This study was 5 to 6 weeks in duration, based on the participants' clozapine blood-monitoring schedule, and it consisted of two 2-week crossover phases separated by a 1- or 2-week washout period. Primary outcome measures included the reduction in the Toronto Nocturnal Hypersalivation Scale (TNHS) and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. Secondary outcomes included visual analog scales assessing hypersalivation severity (VAS-S) and distress (VAS-D). No significant reduction in CIH was found on the TNHS (P = .379), CGI-S (P = .266), or CGI-I (P = .599). Moreover, no difference was noted between study groups on the VAS-S (P = .969) and VAS-D (P = .527). There was no difference in the number of CIH responders at the conclusion of the 2-week placebo (40%, n = 8) and ipratropium (45%, n = 9) study phases (45%, n = 9) according to the TNHS. Randomization order did not have a significant effect on TNHS, CGI-S, or CGI-I scores. Tolerability was comparable between groups, with dry mouth occurring in 1 placebo group subject and 2 ipratropium group subjects. Despite the reports of some preliminary studies that ipratropium is an efficacious treatment for CIH, ipratropium failed to demonstrate significant clinical effect in comparison to placebo. Further research should explore the efficacy of other locally acting anticholinergic agents or other classes of medications. clinicaltrials.gov Identifier: NCT00381589.

Evidence for Efficacy and Tolerability of Vilazodone in the Treatment of Major Depressive Disorder

The efficacy and tolerability of vilazodone, a combined selective serotonin reuptake inhibitor and partial 5-hydroxytryptamine-1A (5-HT(1A)) receptor agonist, were evaluated in adult patients with major depressive disorder (MDD). This was a randomized, double-blind, placebo-controlled trial conducted from February 2006 to May 2007. Patients aged 18 through 65 years with MDD (DSM-IV criteria) and a baseline 17-item Hamilton Rating Scale for Depression (HAM-D-17) score of >or= 22 were randomly assigned to vilazodone or placebo for 8 weeks. Vilazodone was titrated from 10 mg to 40 mg once a day over 2 weeks. Efficacy was assessed by mean change from baseline to week 8 on the Montgomery-Asberg Depression Rating Scale (MADRS), HAM-D-17, and Hamilton Rating Scale for Anxiety. Response rates were determined at week 8 for the MADRS, HAM-D-17, and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. Data were analyzed using a modified last-observation-carried-forward method in the intention-to-treat (ITT) sample. The Arizona Sexual Experience Scale (ASEX) was also measured at baseline and week 8. Of 410 randomly assigned patients, 198 receiving vilazodone and 199 receiving placebo were included in the ITT population. The mean changes in MADRS and HAM-D-17 total scores from baseline to week 8 were significantly (p = .001 and p = .022, respectively) greater with vilazodone than with placebo. Significant (p < .05) improvements in MADRS and HAM-D-17 scores were noted at week 1, the earliest time point measured. Response rates were significantly higher with vilazodone than with placebo on the MADRS (p = .007), HAM-D-17 (p = .011), and CGI-I (p = .001). Treatment-emergent adverse events with vilazodone included diarrhea, nausea, and somnolence; most adverse events were of mild or moderate intensity. There were no clinically significant differences for either gender in ASEX scores at end of treatment. Vilazodone is effective for the treatment of MDD in adults, with symptom relief starting at 1 week, and is well tolerated at a dose of 40 mg/day. clinicaltrials.gov Identifier: NCT00285376.

Placebo-controlled inpatient comparison of venlafaxine and fluoxetine for the treatment of major depression with melancholic features

The objective of this study was to compare venlafaxine and fluoxetine with placebo in treating major depressive disorder with melancholic features. Adult inpatients with Diagnostic and Statistical Manual of Mental Disorders, fourth edition major depressive disorder with melancholia and 21-item Hamilton Depression Rating Scale (HAM-D₂₁) scores > or =24 (n=289) were randomized to receive (double-blind) venlafaxine 225-375 mg/day, fluoxetine 60-80 mg/day, or placebo for 6 weeks. The primary outcome measures were HAM-D₂₁ total score, HAM-D depressed mood item, Montgomery Asberg Depression Rating Scale total score and the Clinical Global Impressions-Severity (CGI-S) and Improvement (CGI-I) scores. Last observation carried forward (LOCF) was the primary analysis method. In the LOCF analysis, venlafaxine was statistically superior to placebo on the CGI-S (venlafaxine -1.7, placebo -1.1; P=0.003) and the HAM-D depressed mood item (venlafaxine -1.6, placebo -1.1; P=0.010); and to fluoxetine on the CGI-S (-1.2; P=0.012). No significant differences were observed on the other 12 LOCF primary efficacy comparisons. Increases in pulse and blood pressure, dry mouth, constipation, and lightheadedness were significantly more common with venlafaxine than fluoxetine. Venlafaxine was statistically superior to placebo on two of five primary and two of five secondary outcome measures and to fluoxetine on one primary and one secondary outcome measure (LOCF). Venlafaxine was not superior to fluoxetine or placebo in providing remission.

Therapeutic effects of escitalopram and reboxetine in seasonal affective disorder: A pooled analysis

The monoaminergic neurotransmitters serotonin and noradrenaline have both been implicated in the pathogenesis of seasonal affective disorder (SAD). However, the differential therapeutic value of selective serotonin reuptake inhibitors (SSRI) and selective noradrenaline reuptake inhibitors (NARI) in SAD has not been assessed until now. This study compares data from two open-label trials with similar methodology investigating the SSRI escitalopram and the NARI reboxetine. 20 SAD patients were treated with escitalopram (10–20 mg) and 15 patients received treatment with reboxetine (fixed dosage: 8 mg) over 6 weeks. Ratings included the structured interview guide for the Hamilton depression rating scale, SAD version (SIGH–SAD), the clinical global impression of severity (CGI-S) and improvement (CGI-I) and the UKU side effect rating scale. Treatment led to a significant reduction in SIGH–SAD score, CGI-S and CGI-I after one week in the reboxetine group and after two weeks in the escitalopram group. SIGH–SAD score was significantly lower in the reboxetine group at weeks 1, 2 and 4 but not at the end of the study. The response rate (SIGH–SAD <50% of baseline value) and the remission rate (SIGH–SAD <8) were not significantly different after 6 weeks of treatment, but the time to response and to remission was significantly shorter in the reboxetine group. The number and severity of side effects were higher in patients treated with reboxetine at all time points. Thus escitalopram and reboxetine were equally effective in treating SAD on all primary and secondary outcome measures. Reboxetine displayed a faster onset of action, but was associated with more pronounced side effects. Further studies comparing SSRI and NARI in SAD are warranted.

An analysis of correlations among four outcome scales employed in clinical trials of patients with major depressive disorder

BackgroundThe 17-item Hamilton Depression Rating Scale (HAM-D17) remains the 'gold standard' for measuring treatment outcomes in clinical trials of depressed patients. The Montgomery Ǻsberg Depression Rating Scale (MADRS), Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I) scales are also widely used.ObjectiveThis analysis of data from 22 double-blind, placebo-controlled clinical studies of venlafaxine in adult patients with major depressive disorder was aimed at assessing correlations among these 4 scales.MethodsChanges from baseline for MADRS, HAM-D17 and CGI-S, and end point CGI-I scores and response (≥50% decrease from baseline HAM-D17 or MADRS, or CGI-S or CGI-I score ≤2) were analysed. Pearson correlation coefficients were calculated for all pairs of the four scales (HAM-D17/MADRS, HAM-D17/CGI-S, HAM-D17/CGI-I, MADRS/CGI-S, MADRS/CGI-I, CGI-S/CGI-I) at different time points. Effect sizes were calculated using the Cohen d.ResultsCorrelations were significant at all time points (p < 0.0001), increased over the course of treatment, and were similar across treatment groups. Effect sizes ranged from 0.31 to 0.42; MADRS and CGI-I effect sizes were slightly greater compared with HAM-D17 or CGI-S for continuous measures and response.ConclusionAlthough MADRS and CGI-I were more sensitive to treatment effects, HAM-D17, MADRS, CGI-S and CGI-I scores present a consistent picture of response to venlafaxine treatment.

Comparative Clinical Responses to Risperidone and Divalproex in Patients with Pediatric Bipolar Disorder

To compare clinical responses of patients with pediatric bipolar disorder being treated with risperidone versus divalproex. Medical records of outpatients younger than 18 years of age were reviewed to gather data on those who received risperidone or divalproex monotherapy for the treatment of bipolar disorder. Effectiveness was assessed using the Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) scales assigned by the treating clinician at visits during the initial 3 months of treatment with risperidone or divalproex. Change in CGI-S score over time was the primary outcome variable. The number of patients with a CGI-I score of < or = 2 at endpoint who did not discontinue the index medication because of adverse events was also compared. A total of 28 patients aged 5-14 years who were being treated for bipolar disorder were identified (risperidone n = 16; divalproex n = 12). Regression analysis of change in CGI-S scores revealed greater reductions in bipolar symptoms (p = 0.022) and a faster reduction in CGI-S scores (p = 0.016) in patients receiving risperidone than divalproex. A significantly shorter time to achieving a CGI-I score of < or = 2 was observed with risperidone than divalproex (26.8 +/- 20.7 days vs. 33.8 +/- 11.3 days; p = 0.048). However, the proportion of patients with a CGI-I score < or = 2 at endpoint was not significantly different (risperidone 69% versus divalproex 42%, p = 0.250). Three patients discontinued risperidone and 2 discontinued divalproex. Of these, none of the patients treated with risperidone and only 1 patient treated with divalproex discontinued treatment because of a documented adverse event. Risperidone was associated with significantly more weight gain then divalproex at 3 months (risperidone 2.46 +/- 1.16 kg versus divalproex 0.43 +/- 0.77 kg, p = 0.034). Patients receiving risperidone experienced a faster decrease in the severity of their bipolar symptoms, as measured by faster decreases in CGI-S scores, than did those who received divalproex. However, risperidone was also associated with significantly greater weight gain.

Escitalopram in a working population: results from an observational study of 2378 outpatients in Austria

The aim of this observational study was to evaluate the effectiveness of escitalopram in a naturalistic sample of employed people with mood and anxiety disorders. Days on sick leave 3 months prior and 3 months during treatment with escitalopram were recorded and compared (mirror study design) in 2378 patients (949 men and 1376 women). A further clinical examination including the clinical global impression of severity (CGI-S) and improvement (CGI-I) scales and assessments of tolerability were used to evaluate treatment effects in a subgroup of 807 study subjects. Escitalopram treatment (mean final daily dosage: 12.4+/-5.0 mg) led to a significant reduction (baseline versus end of study) of sick leave (11.0+/-12.8 days versus 5.4+/-11.0 days; p<0.001). CGI-S scores decreased from 4.7+/-0.9 at baseline to 2.4+/-1.1 after 3 months (p<0.001), the CGI-I after 3 months was 1.9+/-0.9. The incidence of adverse events after initiation of treatment with escitalopram was 13.1%, with only 1.3% of patients experiencing severe adverse events interfering with patient functioning. Our results suggest that escitalopram is an efficacious and overall well-tolerated treatment in a naturalistic sample of working patients. A decrease in the days on sick leave is indicative of indirect cost-effectiveness of this treatment.

Agomelatine in the treatment of seasonal affective disorder

The novel antidepressant agomelatine acts as a melatonergic (MT(1) and MT(2)) receptor agonist and as a serotonin-2C receptor antagonist. Previous studies showed that agomelatine is able to restore disrupted circadian rhythms, which were implicated in the pathophysiology of seasonal affective disorder (SAD). The aim of this study was to investigate the efficacy and tolerability of agomelatine in the treatment of SAD. Thirty-seven acutely depressed SAD patients were included in an open study with agomelatine (25 mg/day in the evening) over 14 weeks. Efficacy assessments included the Structured Interview Guide for the Hamilton Depression Rating Scale (SAD version; SIGH-SAD), the Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I), the Circscreen, a self-rating scale for the assessment of sleep and circadian rhythm disorders, and the Hypomania Scale. Agomelatine led to a progressive and statistically significant decrease of SIGH-SAD, CGI-S, and CGI-I scores from week 2 onward (p < 0.001). Furthermore, scores on the Circscreen improved significantly during the study (p < 0.001). Treatment with agomelatine over 14 weeks yielded a response rate of 75.7% (SIGH-SAD <50% of baseline value) and a remission rate (SIGH-SAD <8) of 70.3% in the intention to treat sample. Scores on the Hypomania Scale were consistently low during the study. Agomelatine showed good overall tolerability: throughout the study only one adverse event (mild fatigue) was related to the study drug. The results of this study suggest that seasonal depression may be effectively and safely treated with agomelatine.

Improvement in antipsychotic-related metabolic disturbances in patients with schizophrenia switched to ziprasidone

Purpose This study evaluated changes in weight, glucose and lipid metabolism in patients with schizophrenia and antipsychotic-related metabolic disturbances who were switched to ziprasidone. Methods Eighty-four outpatients with schizophrenia or schizoaffective disorder also having glucose intolerance, diabetes, dyslipidemia or weight gain related to their antipsychotic treatment were switched to ziprasidone. Clinical status was assessed using the Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I) scales and the Positive and Negative Syndrome Scale (PANSS). Assessment scales, weight, glucose and lipids were measured at baseline and at three and six months of ziprasidone treatment. Results Significant baseline to endpoint reductions were seen in mean weight (− 5.1 kg), Body Mass Index (BMI; − 1.6 kg/m 2), serum glucose (− 14.0 mg/dL), total cholesterol (− 24.1 mg/dL), and triglyceride leves (− 46.2 mg/dL). Mean PANSS total score improved 13.9% after 6 months of treatment with ziprasidone. A proportion (34.3%) of patients were classified as much improved in the CGI-I. Conclusions Switching patients with schizophrenia to ziprasidone when metabolic disturbances are detected may improve these side effects and result in an improved overall outcome.

Open-Label Trial of Escitalopram in the Treatment of Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a highly prevalent, disabling illness. Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication treatment, with sertraline, paroxetine, and fluoxetine being the most studied. More limited but favorable data suggest that citalopram, an SSRI, may also have a role in the treatment of PTSD. Its S-enantiomer escitalopram, which may have faster onset and greater magnitude of effect than citalopram in other conditions, has not yet been investigated in PTSD. To assess the efficacy, safety, and tolerability of escitalopram in the treatment of PTSD. A 12-week, prospective, open-label trial of escitalopram was conducted from January 2003 through August 2004 in military veterans with PTSD. Escitalopram was initiated at 10 mg daily for 4 weeks, then increased to 20 mg daily for the remainder of the study. Concomitant psychiatric medications were discontinued at least 2 weeks prior to enrollment. The primary outcome variable was the change from baseline to endpoint in global Clinician-Administered PTSD Scale-Symptom version (CAPS-SX) score. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, the Hamilton Rating Scale for Depression (HAM-D), and the Davidson Trauma Scale (DTS). Posttraumatic stress disorder and comorbid diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Twenty-four of 25 patients were evaluated for efficacy. The mean global CAPS-SX score decreased from 79.4 (SD = 15.7) at baseline to 61.2 (SD = 24.7) at the end of the study (p = .0002). The CAPS-C avoidance/numbing and CAPS-D hyper-arousal subscale scores decreased significantly from baseline to endpoint (CAPS-C, p = .0171; CAPS-D, p = .0001), with trend-level reductions observed in CAPS-B reexperiencing subscale scores (p = .0593). Forty-five percent of patients (9/20) were much or very much improved at the end of the study (CGI-I of 1 or 2). The HAM-D and DTS also significantly improved (p = .0063 and p = .0004, respectively). Mild to moderate gastrointestinal disturbances were the most common side effects. Only 4 patients discontinued early because of adverse effects. This preliminary open-label study suggests that escitalopram is both efficacious and well tolerated in PTSD patients. However, randomized controlled studies are needed to confirm these results and to further define its potential role in the treatment of PTSD.

The Influence of Baseline Severity on Efficacy of Escitalopram and Citalopram in the Treatment of Major Depressive Disorder: An Extended Analysis

To determine the differences between escitalopram and citalopram in the treatment of patients with major depressive disorder across a range of baseline severity of depression using trend analysis. Data from the three placebo-controlled studies comparing escitalopram to citalopram were analyzed. The pre-specified primary outcome variable was MADRS total score; secondary outcomes included Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) scores. All analyses were based on an intent-to-treat (ITT) population and all direct comparisons were done by ANCOVA adjusting for baseline value and centre. Analyses of the pooled data (N=1203) show that, while the difference between citalopram and placebo was approximately constant across the range of baseline severity, the difference between escitalopram and placebo (p=0.0010 for no trend) and between escitalopram and citalopram (p=0.0012 for no trend) became greater, the more severely depressed the patients were at baseline. A similar pattern was apparent with the CGI-S and CGI-I results. There was a significant superiority of escitalopram over citalopram in response rate (defined as > or = 50% decrease in MADRS total score), and this difference increased with increasing baseline severity. These trend analyses thus indicate that the superiority of escitalopram over citalopram is more apparent as the baseline severity of depression increases.

An Analysis of Correlations Among 4 Outcome Scales Employed in Clinical Trials of Patients With Major Depressive Disorder

Introduction The objective of this analysis was to identify and assess any correlations among 4 widely used rating scales—the17-item Hamilton Depression Rating Scale (HAM-D17), the Montgomery-Asberg Depression Scale (MADRS), the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I)—in clinical trials with patients with major depressive disorder (MDD). Methods Data from 22 randomized, double-blind, placebo-controlled venlafaxine studies (10 ER studies, 11 IR studies, 1 with both formulations) in adult patients with MDD were pooled and examined from baseline through the first 8 weeks of treatment. For all rating scales, Pearson correlation coefficients were calculated between change scores and by treatment arm for patients at each visit. Correlations between binary outcomes (response defined as CGI-I and CGI-S ≤ 2, 50% decrease in HAM-D17 and MADRS) were determined. Results At pretreatment visits, for the HAM-D17, MADRS, and CGI-S, respectively, 5117, 4871, and 5103 observations were available, with mean scores of 23.0, 29.1, and 4.4. Pretreatment correlations ranged from 0.52 (CGI-S and HAM-D17), 0.53 (CGI-S and MADRS), and 0.62 (HAM-D17 and MADRS). Correlations between scales increased at each visit and, at 8 weeks, ranged from 0.87 (CGI-S and CGI-I) to 0.93 (HAM-D17 and MADRS). Correlation coefficients in treatment arm subgroup analyses and between change scores were comparable. Correlation coefficients between binary outcomes were lower, ranging from 0.42 (CGI-I and CGI-S) to 0.61 (HAM-D17 and MADRS) at week 1 and from 0.61 (CGI-I and CGI-S) to 0.81 (HAM-D17 and MADRS) at week 8. All correlation coefficients were significant (P Conclusions Correlations among the four commonly used outcome scales were high; however, correlations among binary outcomes based on the scales were lower. The highest correlations were between the HAM-D17 and the MADRS, which share several items and have similar modes of administration and rating. The modest but consistently lower correlations between the CGI-S and CGI-I scales were unexpected because these scales are sometimes considered interchangeable.

Randomized Clinical Trial of Telepsychiatry through Videoconference versus Face-to-Face Conventional Psychiatric Treatment

Although telepsychiatry in the form of videoconferencing has been well received in terms of increasing access to care and user satisfaction, few data on treatment outcomes and efficacy from telepsychiatry applications are available at the present time. This paper evaluates the efficacy of telepsychiatry through videoconference in the treatment of mental disorders by comparing to face-to-face conventional (F2FC) treatment. We carried out a randomized clinical trial where 140 psychiatric outpatients were randomized to either F2FC treatment or videoconference telepsychiatry (VCTP) treatment. Patients were diagnosed according to International Classification of Diseases, 10th edition (ICD-10) criteria using the Composite International Diagnostic Interview. Treatment involves eight consultations lasting 30 minutes over the 24-week study period. Patients received pertinent psychotropic medication plus cognitive- behavioral therapy during sessions. The same psychiatrist diagnosed and treated all the patients that were recruited from the Community Mental Health Centre of San Sebastian de la Gomera, in the Canary Islands. Change in psychiatric test scores served as the primary efficacy criterion. Efficacy was determined by comparing baseline (visit 1) Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales as well as Global Indexes (GSI, PSDI, and PST) from SCL-90R with scores obtained at the end of the study period (week 24). Response was defined as a CGI-I score of 1 or 2. Reliable Change Indexes were computed in SCL-90R Global Indexes scores. Of 140 patients randomized, 130 completed 24 weeks of treatment. Only 4 patients dropped out prematurely from the study in VCTP and 6 in F2FC. The study involves 534 teleconsultations, 522 F2FC consultations, and more than 500 hours of clinical practice. Significant improvements were found on the CGI and SCL-90- R Global Indexes scores of both treatment groups, showing clear clinical state improvement. No statistically significant differences were observed when the efficacy of VCTP treatment was compared to F2FC psychiatric treatment efficacy. This study demonstrated that telepsychiatry treatment through videoconference has equivalent efficacy to F2FC psychiatric treatment. Telepsychiatry showed to be an effective mean of delivering mental health services to psychiatric outpatients living in remote areas with limited resources.

Venlafaxine Extended Release in the Short-Term Treatment of Depressed and Anxious Primary Care Patients With Multisomatoform Disorder

This pilot study explored the efficacy and tolerability of extended-release venlafaxine (venlafaxine ER) in anxious and/or depressed patients with multisomatoform disorder (MSD). This 12-week, multicenter, randomized, double-blind study evaluated adult primary care outpatients with MSD and comorbid major depressive disorder, generalized anxiety disorder, or social anxiety disorder (DSM-IV criteria). The intent-to-treat population included 112 patients (venlafaxine ER, N = 55; placebo, N = 57). The primary efficacy variable was the change in the 15-item Patient Health Questionnaire (PHQ-15) somatic symptom severity score. Secondary outcomes included the Hamilton Rating Scale for Depression (HAM-D-17) and for Anxiety (HAM-A), Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, McGill Quality of Life Questionnaire Physical Symptoms Scale (MQOL-PS), and Medical Outcomes Study Short-Form 36-Item questionnaire (MOS SF-36). Data were collected from April 2003 to December 2003. The decline by week 12 in PHQ-15 scores was significant (p < .0001) in both groups; however, the difference between the venlafaxine ER and placebo groups (-8.3 vs. -6.6, respectively) was not (p = .097). Improvement was greater with venlafaxine ER than placebo on the PHQ-15 pain subscale (p = .03), SF-36 bodily pain scale (26.1 vs. 14.5, p = .03), MQOL-PS (-11.7 vs. -6.0, p = .02), HAM-A psychic anxiety subscale (p = .02), SF-36 mental component summary (p = .03), time to response (54 vs. 71 days, p = .01), and CGI-I scale (p = .009). Venlafaxine ER was generally well tolerated. These results suggest that venlafaxine ER may be effective in relieving some types of somatic physical symptoms, particularly pain, in patients with depression and/or anxiety disorders.