Duloxetine in the treatment of irritable bowel syndrome: an open-label pilot study.

OBJECTIVE: To assess the efficacy of duloxetine for irritable bowel syndrome (IBS). METHODS: We conducted an open-label 12-week trial of duloxetine 60 mg daily in 15 patients with IBS without concurrent major depressive disorder. The primary outcome measure was average abdominal pain. Secondary measures included IBS symptoms, Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, IBS Quality-of-Life Scale, and Sheehan Disability Scale. We analyzed changes using random regression and one-sample t-tests. RESULTS: Fourteen patients completed at least one post-baseline evaluation; eight completed the study. Duloxetine was associated with significant improvement (p < 0.05) in pain, severity of illness, quality of life, loose stool, work and family disability, and anxiety. However, duloxetine did not improve hard stool. Although we found no evidence of serious duloxetine toxicity, seven participants withdrew over the course of the study because of adverse drug events. CONCLUSIONS: In this small, open-label study, duloxetine appeared to be effective for many features of IBS, but its adverse effects, most notably constipation, limited its use. Since our study excluded individuals with concurrent major depression, it appears that duloxetine may benefit IBS independently of its antidepressant effects. These encouraging but preliminary open-label findings support further investigation of duloxetine treatment in placebo-controlled trials of IBS.

Memantine in the treatment of binge eating disorder: an open-label, prospective trial.

OBJECTIVE: To assess preliminarily the efficacy of memantine in binge eating disorder. METHOD: This was an open-label, 12-week, flexible-dose (5-20 mg/day) trial of memantine in binge eating disorder. The primary outcome was frequency of binge days. Secondary outcomes included frequency of binge episodes, body-mass index (BMI), weight, Clinical Global Impressions Severity (CGI-S), Three Factor Eating Questionnaire (TFEQ), Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Sheehan Disability Scale (SDS). Longitudinal random regression analysis was performed for frequency of binge days and episodes, BMI, weight, and CGI-S; analysis of baseline to endpoint change was performed for all outcomes. RESULTS: Sixteen individuals received memantine; 15 completed at least one postbaseline evaluation, 9 completed the study. Mean dose at endpoint was 18.3 mg/day. Memantine was associated with significant reductions in frequency of binge days and episodes, severity of illness (p < .001 for both analyses), disinhibition on the TFEQ (p = .015), and disability on the SDS (p < .05 for three subscales). There was no significant change in BMI, weight, MADRS, HAM-A, and TFEQ cognitive restraint and hunger. CONCLUSION: In this open-label trial, memantine was well tolerated and effective in reducing binge eating, severity of illness, and disability, but had little effect on BMI and weight.

Aripiprazole: initial clinical experience with 142 hospitalized psychiatric patients.

BACKGROUND: Aripiprazole is the first dopamine D2 receptor partial-agonist approved for treatment of schizophrenia. Its apparently benign adverse-effect profile encourages broader use in other disorders, especially to limit weight gain associated with other antipsychotic or antimanic agents. We considered the first 6 months of experience with aripiprazole in psychiatric inpatients with a range of disorders. METHODS: We analyzed data obtained from medical records of patients treated with aripiprazole who were hospitalized at McLean Hospital (for 19 +/- 18 days) between December 2002 and June 2003 to evaluate dosing, tolerability, and clinical effects of this new agent in patients diagnosed with DSM-IV psychotic, major affective, or other disorders. RESULTS: Out of a sample of 2766 adult inpatients (65.5% women), 142 were given aripiprazole (mean final daily dose, 16.1 +/- 6.2 mg, 0.20 +/- 0.09 mg/kg body weight) for major affective disorders (52%), primary psychotic disorders (40%), and dementia (8%). CGI ratings improved by 20% on average. Adverse effects were infrequent (15.5%), were three times more likely among women, and most often involved moderate behavioral activation or nausea, with no new episodes of mania. Of the patients who were given aripiprazole, 83% continued it at discharge. Many patients were obese when they were admitted, and obesity was associated with relatively low mg/kg doses of aripiprazole. CONCLUSIONS: Aripiprazole was used in a range of disorders and was generally well tolerated. Adverse effects may reflect its unique dopamine partial-agonist activity. Since aripiprazole is likely to be considered for obese patients, body weight should be considered in establishing adequate doses. Controlled trials of this antipsychotic agent in disorders other than schizophrenia are needed.

Pilot comparison of extended-release and standard preparations of divalproex sodium in patients with bipolar and schizoaffective disorders.

OBJECTIVE: The authors compared the new extended-release and standard preparations of divalproex sodium. METHOD: Twelve patients with DSM-IV bipolar disorder or schizoaffective disorder who were clinically stable while taking the standard form of divalproex participated in the study. These patients were given a single daily dose of the extended-release preparation of divalproex in an open 6-week trial. Clinical symptoms and adverse effects were rated weekly. Doses were adjusted to maintain steady serum valproate concentrations. RESULTS: The medication change was associated with negligible changes in clinical status and tolerability. To maintain serum drug levels, however, 21% higher doses of the extended-release preparation were required. CONCLUSIONS: Use of extended-release divalproex once a day was as well tolerated as the standard preparation, with no change in efficacy within 6 weeks, but the daily dose needed to maintain stable serum valproic acid concentration was 21% higher.

Ziprasidone: first year experience in a hospital setting.

BACKGROUND: The antipsychotic drug ziprasidone, FDA-approved and introduced in the United States in February 2001 for the treatment of schizophrenia, appears to have similar efficacy but better tolerability than older antipsychotics and requires further evaluation under clinical conditions. METHODS: We analyzed medical records of McLean Hospital inpatients treated with ziprasidone between March 2001 and February 2002, gathering data on DSM-IV diagnoses, presenting symptoms, dosing, concomitant psychotropic medications, clinical changes, adverse effects, and electrocardiographic (ECG) findings. RESULTS: Ziprasidone was given to 151 inpatients (3.4% of admissions; 108 women, 43 men), aged 37.5 +/- 11.4 years, who presented with depression (n = 79), psychosis (n = 46), mania (n = 18), bipolar mixed-states (n = 4), or other conditions (n = 4). Daily doses averaged 49.8 +/- 34.1 mg initially and 83.2 +/- 46.3 mg at discharge; the greatest dose increases during hospitalization (by a mean of 61%) were in patients with schizoaffective disorder (n = 46; 30% of cases). In 41 cases (27%), ziprasidone was the only antipsychotic at discharge; in 61 (40%) it was used with other antipsychotics. Ziprasidone was discontinued during hospitalization in 49 cases (32.5%), due to lack of efficacy (n = 26; 17.2%), adverse effects (n = 13, 8.6%), or reasons not stated (n = 10, 6.6%). Of 70 patients for whom ECG data were obtained during treatment with ziprasidone, 8 (11%) had QTc intervals > 450 msec during treatment, but none of the 39 patients with ECGs both before and during ziprasidone treatment showed clinically meaningful increases in QTc intervals. Ziprasidone was discontinued in 4 patients (2.6%) due to concern about QTc intervals, but in no case was the QTc interval > or = 500 msec or associated with clinical cardiac toxicity. Improvements in CGI and GAF scores from admission to discharge were similar across diagnoses and unrelated to length of stay or ziprasidone dose. CONCLUSIONS: Ziprasidone was well tolerated by hospitalized patients with various major psychiatric disorders and may be of value in conditions other than schizophrenia.

Hospital use of antipsychotic drugs: polytherapy.

OBJECTIVE: Growing acceptance of new psychotropic drugs encouraged a survey of current use of antipsychotic drugs alone and in combinations, with comparisons with previous findings. METHOD: Records from a random sample of McLean Hospital (Belmont, Mass) inpatients treated with an antipsychotic from March to May 2004 were reviewed for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, discharge diagnosis; all current psychotropic drug treatments; initial, peak, and final chlorpromazine-equivalent milligram-per-day dose of antipsychotics (APD); initial, peak, and final lithium-equivalent dose (milligram per day) of mood stabilizers (MS); weight change; clinical status at admission and discharge; and days of hospitalization. RESULTS: In the 305 inpatients sampled (n = 184 women, 60.3%), Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, clinical conditions ranked as follows: major affective (n = 161, 52.8%), psychotic (n = 99, 32.5%), and other disorders (n = 45, 14.8%). Modern drugs comprised 92% of antipsychotic prescriptions, and quetiapine (usually at low doses) was most frequently prescribed. "Polytherapy" (simultaneous treatment with > or =2 psychotropic agents) at discharge was identified in 80% of antipsychotic-treated patients. Use of at least 2 antipsychotics (in 23% of cases) was associated with a 2.8-fold increase in total dose vs monotherapy (651 +/- 403 vs 232 +/- 205 mg/d). Total antipsychotic doses also were higher with mood stabilizer (most often divalproex) or sedative (usually high-potency benzodiazepine) cotreatment, use of older neuroleptics, psychotic-disorder diagnoses, and substance use comorbidity. Polytherapy was not associated with superior clinical improvement or shorter hospitalization but was associated with higher body weight. CONCLUSIONS: Polytherapy involving antipsychotic drugs continues to increase despite limited empirical evidence for greater effectiveness or of safety of such combinations.

Antipsychotic drug use: McLean Hospital, 2002.

OBJECTIVE: Major changes in antipsychotic treatment in recent years encouraged a survey of inpatient practice in 2002, compared with earlier samples. METHODS: Based on records of a random sample of McLean Hospital inpatients prescribed antipsychotics in 2002, the study recorded DSM-IV discharge diagnosis, all psychotropic treatments and doses, initial, peak and final doses of all antipsychotics, clinical status at admission and discharge, and adverse effects reported. Results were compared with similar data from our earlier surveys. RESULTS: Subjects were 344 inpatients (n = 202 women, 59%), diagnosed with psychotic (n = 102, 30%), bipolar (n = 93, 27%), major depressive (n = 67, 19.5%), dementia (n = 19, 5.5%), substance-use (n = 28, 8%) or other psychiatric disorders (n = 35, 10%). Second-generation antipsychotics accounted for 88% of antipsychotic prescriptions; 17% of patients received > or = 2 antipsychotics and total CPZ-eq discharge does in 2002 averaged 291 +/- 305 mg/day (22% less than a 1998 peak). Doses were unrelated to age, but higher in men, among psychotic vs major affective disorder patients, and with greater illness-severity and longer hospitalization. There was a 3.3-fold increase in the simultaneous use of > or = 3 psychotropic agents since 1998. CONCLUSIONS: The use of second-generation antipsychotics dominates current inpatient practice. Total antipsychotic dosing has not increased recently, but the use of multiple psychotropics increased strikingly from 1998 to 2002.

Use of combinations of antipsychotics: McLean Hospital inpatients, 2002.

BACKGROUND: The empirical use of combinations of antipsychotic agents appears to be increasing with little research support for the relative efficacy, safety or cost-effectiveness of this practice. Such treatment was evaluated in hospitalized psychiatric patients. METHODS: Samples of consecutive inpatients treated with > or = 2 ('polytherapy') vs 1 antipsychotic ('monotherapy') were matched on age, sex, diagnosis and admission clinical ratings, and these groups were compared on total daily chlorpromazine-equivalent doses, days in hospital, and changes in clinical ratings between admission and discharge. RESULTS: The study sample included 69 polytherapy and 115 well-matched monotherapy subjects. Despite matching for initial CGI and GAF ratings, polytherapy was associated with high PANSS subscale scores of positive symptoms among affective psychosis, and relatively greater PANSS subscale ratings of excitement-agitation among patients diagnosed with schizophrenia. Estimated clinical improvement during hospitalization was similar among poly- and monotherapy patients, but total daily CPZ-eq doses at discharge averaged twice-greater with polytherapy, and hospitalization lasted 1.5 times longer. CONCLUSIONS: Antipsychotic polytherapy as well as the types of agents combined may reflect clinician responses to particular symptom patterns. The value of specific combinations of antipsychotic agents and their comparison with monotherapies requires specific, prospective, randomized and well-controlled trials that consider matching on clinical characteristics and truly comparable doses across regimens.

Oxcarbazepine: clinical experience with hospitalized psychiatric patients.

BACKGROUND: Oxcarbazepine (10-keto-carbamazepine) appears to be better tolerated and simpler to use than carbamazepine. It has antimanic effects but, as its potential clinical usefulness and tolerability in broad samples of psychiatric patients remain to be tested, we reviewed both the pharmacology of oxcarbazepine and our early experience with this new agent among psychiatric inpatients. METHODS: We reviewed medical records of all inpatients given oxcarbazepine in the first 15 months of its use at McLean Hospital. Data analyzed included dosing, presenting illnesses, other medications, clinical changes, and adverse effects. RESULTS: Oxcarbazepine was given to 56 inpatients (1.3% of admissions; 31 women, 25 men) presenting with depression (n = 23), mania (n = 19), or psychosis (n = 14). The discharge daily dose for the 43 patients (76%) taking oxcarbazepine was 831 mg/day, 34% higher in men than women, and fell by 9 mg/year-of-age. Oxcarbazepine was the only putative mood-stabilizing agent given at discharge in 19 of 43 cases (44%). It was discontinued in 20% of patients for apparent inefficacy, and 4% for adverse effects. Changes in CGI and GAF scores were similarly high across illnesses, and unrelated to days of use of oxcarbazepine or its dose. CONCLUSIONS: Oxcarbazepine was well tolerated and simpler to use clinically than its precursor carbamazepine. This agent should be studied in controlled trials to test its efficacy in specific types of major psychiatric disorders, and particularly for long-term maintenance treatment in bipolar disorder.