Showing papers in "Journal of Clinical Psychopharmacology in 2006"

Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study).

Abstract: :This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (30

The status of disulfiram: a half of a century later.

Abstract: For more than 55 years, disulfiram has been approved by the Food and Drug Administration for the treatment of alcohol dependence. It is a unique medication that relies on "psychological threat" to avoid disulfiram-ethanol reactions. This paper reviews the history of disulfiram treatment, the current status of disulfiram treatment, the ensuing developments in disulfiram use in treating various addictions, and future directions. Clinical trials using disulfiram for the treatment of alcohol, cocaine, or co-occurring alcohol + cocaine dependence were included in this review. Disulfiram efficacy studies focusing on supervised, implant, and combination pharmacotherapies were also examined. In clinical trials, disulfiram has demonstrated inconsistent results in helping patients to abstain from alcohol, and patients poorly adhere to a disulfiram-treatment regimen. This has raised questions about disulfiram's practicality in the treatment of alcohol dependence. Recently, however, disulfiram has gained attention as a complementary agent to newer pharmacological medications, such as an opiate antagonist that specifically reduces alcohol craving. One hypothesis is that disulfiram would assist patients in gaining psychological control over drinking when given in conjunction with an opiate antagonist that would act directly on reducing alcohol craving. Preliminary evidence also suggests that disulfiram treatment could be a viable treatment for cocaine dependence because it was shown to reduce cocaine use among nonalcoholic, cocaine-dependent patients.

The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking.

Abstract: Background:In almost 2 decades of naltrexone research for treating alcoholism, there have been 29 published randomized placebo-controlled trials of opioid antagonists, primarily naltrexone, for the treatment of alcohol dependence. The present review builds on prior systematic reviews while maximizin

Postpartum depression: a randomized trial of sertraline versus nortriptyline.

Abstract: Symptom reduction and improvement in functioning in women with postpartum major depression treated with a tricyclic antidepressant versus a serotonin reuptake inhibitor were compared. The design was a double-blind, 8-week comparative trial of nortriptyline (NTP) versus sertraline (SERT) with a 16-week continuation phase. Women aged 18 to 45 years with postpartum major depression and a 17-item Hamilton Rating Scale for Depression score of 18 or more were eligible. Subjects were randomized to NTP or SERT and treated with a fixed-dosing strategy. Of 420 women interviewed, 109 eligible women received medication, and 95 provided follow-up data. The proportion of women who responded and remitted did not differ between drugs at 4, 8, or 24 weeks. Times to response and remission also did not differ. Psychosocial functioning improved similarly in both drug-treated groups of mothers. The total side effect burden of each drug was similar, although side effect profiles differed between agents. No clinical or demographic variables differentiated responders by drug. Women who were responders and remitters at week 8 could be identified earlier if they were treated with SERT than with NTP. Breast-fed infant serum levels were near or below the level of quantifiability for both agents.

Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study.

Abstract: This 12-week, double-blind, multicenter trial evaluated the efficacy of venlafaxine extended release (ER), sertraline, and placebo in adult outpatients (N = 538) with a primary diagnosis of posttraumatic stress disorder (PTSD), as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, symptoms for 6 months or more and 17-item Clinician-administered PTSD Scale (CAPS-SX17) score of 60 or more. Patients were randomly assigned to receive placebo or flexible doses of venlafaxine ER (37.5-300 mg/d) or sertraline (25-200 mg/d) for 12 weeks or less. The primary outcome was the baseline-to-end point change in total CAPS-SX17 score (last observation carried forward). Secondary measures included CAPS-SX17 symptom cluster scores for reexperiencing/intrusion, avoidance/numbing, and hyperarousal; frequency of remission (CAPS-SX17 < or =20); and changes in Davidson Trauma Scale total score and symptom cluster scores for avoidance/numbing, hyperarousal, and reexperiencing/intrusion. Mean changes in CAPS-SX17 scores were -41.8, -39.4, and -33.9 for venlafaxine ER (P < 0.05 vs. placebo), sertraline, and placebo, respectively. Mean changes for venlafaxine ER, sertraline, and placebo in CAPS-SX17 cluster scores were -13.0, -11.7, and -11.0 for reexperiencing; -17.1, -16.8, and -13.7 (P < 0.05 both active treatments vs. placebo) for avoidance/numbing; and -11.8, -10.9, and -9.2 (P < 0.05 venlafaxine vs. placebo) for hyperarousal. Week 12 remission rates were venlafaxine ER 30.2% (P < 0.05 vs. placebo), sertraline 24.3%, and placebo 19.6%. The venlafaxine ER group had significantly better Davidson Trauma Scale total and cluster scores than placebo. Mean maximum daily doses were 225-mg venlafaxine ER and 151-mg sertraline. Both treatments were generally well tolerated. Study results suggest that venlafaxine ER is effective and well tolerated in the short-term treatment of PTSD.

A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression.

Abstract: We examined the efficacy and tolerability of augmentation with an extended release formulation of methylphenidate (OROS MPH, Concerta) in patients with major depression who were nonresponders or partial responders to antidepressants. Sixty subjects with treatment-resistant depression (TRD) participated in a 4-week, randomized, double-blind, placebo-controlled study of augmentation with methylphenidate (18-54 mg/d). The preexisting antidepressant dose was unchanged. The primary efficacy measure was change in the 21-item Hamilton Depression Rating Scale from randomization to end of treatment. Data were analyzed with intent-to-treat with last observation carried forward approach. There were no statistically significant differences between the methylphenidate (n = 30) and placebo (n = 30) groups in reduction in 21-item Hamilton Depression Rating Scale scores (drug, -6.9; placebo, -4.7) from baseline to end of treatment (F1,47 = 1.24, P = 0.22), although responders were numerically higher in the extended-release methylphenidate group (40.0%) than in the placebo group (23.3%). On the secondary efficacy measures of changes in Clinical Global Impression-Improvement and Severity scores and Beck Depression Inventory-Second Edition, the drug failed to separate from placebo, although the proportion of responders in the drug group were numerically higher than placebo. There were no significant differences in weight, heart rate, and blood pressure changes between the 2 groups. The common adverse events were loss of appetite, nausea, headache, and anxiety. The mean dose of drug was 34.2 mg/d. The study did not demonstrate a statistically significant benefit for augmentation with methylphenidate in TRD. Combination of methylphenidate with antidepressants was well tolerated. Adequately powered, randomized, controlled trials are necessary to fully evaluate the efficacy of extended-release methylphenidate in TRD.

Risperidone-related weight gain: genetic and nongenetic predictors.

Abstract: Objective:A serious side effect of atypical antipsychotics is increased body weight, which leads to further morbidity and nonadherence to medication. It has been suggested that both genetic and nongenetic variables may influence antipsychotics-related weight gain. This study aimed to simultaneously

Remission and relapse in the outpatient care of schizophrenia: three-year results from the Schizophrenia Outpatient Health Outcomes study.

Abstract: Remission and relapse are clinical outcomes of increasing interest in schizophrenia. We analyzed remission and relapse, and the sociodemographic and clinical factors associated with these outcomes, in the usual care of schizophrenia using the 3-year, follow-up data from a large cohort of outpatients with schizophrenia taking part in the prospective, observational, European Schizophrenia Outpatient Health Outcomes study. Of the 6516 patients analyzed for remission, 4206 (64.6%) achieved remission during the 3-year, follow-up period. Logistic regression analysis revealed that being female, having a good level of social functioning at study entry, and a shorter duration of illness were factors significantly associated with achieving remission. Treatment with olanzapine was also associated with a higher frequency of remission compared with other antipsychotic agents. A Kaplan-Meier survival curve estimated that relapse occurred in approximately 25% of the patients who achieved remission, with the risk of relapse remaining constant during the follow-up period. Shorter duration of illness, having hostile behaviors, and substance abuse were factors associated with a higher risk of relapse, whereas good level of social functioning and the use of olanzapine and clozapine were associated with a lower risk of relapse. In conclusion, the 3-year results of the Schizophrenia Outpatient Health Outcomes study indicate that the likelihood of remission decreases over the longitudinal course of schizophrenia, but risk of relapse is maintained even after 3 years of achieving remission severity levels. Results suggest that treatment with olanzapine is associated with a better chance of achieving remission than other antipsychotics. Moreover, the use of olanzapine and clozapine is associated with a lower risk of relapse compared with risperidone, quetiapine, and typical antipsychotics. The results should be interpreted conservatively because of the observational, nonrandomized study design.

Safety and efficacy of escitalopram in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomized study.

Abstract: Purpose:To evaluate the efficacy and safety of most selective serotonin reuptake inhibitor drug, escitalopram, in delaying ejaculation in patients with premature ejaculation (PE).Materials and Methods:A total of 276 married men (mean age, 34.4 years) with PE were randomly assigned to receive 10 mg o

Suicide rates in short-term randomized controlled trials of newer antidepressants.

Abstract: Concerns have been raised about the appropriateness of placebo controls in clinical trials for major depressive disorder (MDD), given that there are approved treatments for this illness. Critics have argued that patients with untreated depression would be exposed to an unnecessary risk of suicide. There is also a competing concern that antidepressant drug treatment itself may induce suicidal behavior and thinking (suicidality). To examine this question, we have evaluated the rate of suicide in placebo- and active drug-treated groups of patients with MDD and various anxiety disorders participating in short-term randomized controlled trials (RCTs). We examined data from all manufacturer-sponsored short-term RCTs of 9 commonly used antidepressants in patients with MDD and various anxiety disorders. All short-term RCTs of antidepressants in patients with MDD and various anxiety disorders were included. Individual patients' data were available for all trials. Data were available for the 207 trials conducted in patients with MDD, including a total of 40,028 patients. There were 21 cases of suicide in these patients. Forty-four trials were conducted in patients with various anxiety disorders, including a total of 10,972 patients. There were 2 cases of suicide in these patients. Overall, at least 1 case of suicide occurred in 21 of the 251 trials. Sixteen of the suicides in MDD trials occurred in trials that had only an active control comparison group, and most of these (14 cases) were observed in the non-North American trials. In the placebo-controlled MDD trials, the rate ratios of suicide in the combined drug groups compared with placebo were 1.07 (0.1-63.4) and 0.5 (0.0-36.7) for the non-North American and North American trials, respectively. In the anxiety disorder studies, the overall rate ratio of suicide for the selective serotonin reuptake inhibitors compared with placebo was 0.9 (0.0-71.4). Neither use of placebo nor of antidepressants in short-term RCTs was associated with an increased risk of completed suicide among patients with MDD or various anxiety disorders. Nonetheless, because of the small numbers of suicides in these trials and the subsequent lack of statistical power, an increased risk of completed suicide in association with either drug or placebo treatment cannot be definitively excluded.

A Meta-Analysis of Early Sustained Response Rates Between Antidepressants and Placebo for the Treatment of Major Depressive Disorder

Abstract: Context:Pattern analysis suggests that "true" drug response is characterized by clinical improvement that is not subsequently followed by a worsening of symptoms (sustained clinical response) To date, several reports demonstrate that early response rates are equivalent between antidepressant-treate

Topiramate treatment for women with borderline personality disorder: a double-blind, placebo-controlled study.

Abstract: Borderline personality disorder is a common and severe psychiatric illness. The goal of this study was to determine whether topiramate can influence patients' borderline psychopathology, health-related quality of life, and interpersonal problems. Women meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Structured Clinical Interview II criteria for borderline personality disorder were randomly assigned in a 1:1 ratio to topiramate titrated from 25 to 200 mg/d (n = 28) or placebo (n = 28) for 10 weeks. Primary outcome measures were changes on the Symptom-Checklist, on the SF-36 Health Survey, and on the Inventory of Interpersonal Problems. Body weight and additional side effects were assessed weekly. According to the intent-to-treat principle, significant changes (all P < 0.001) on the somatization, interpersonal sensitivity, anxiety, hostility, phobic anxiety, and Global Severity Index scales of the Symptom Checklist were observed in the topiramate-treated subjects after 10 weeks (no significant changes on the obsessive-compulsive, depression, paranoid ideation, and psychoticism scales). In the SF-36 Health Survey, significant differences were observed on all 8 scales (all P < 0.01 or P < 0.001). In the Inventory of Interpersonal Problems, significant differences (all P < 0.001) were found in the scales for overly autocratic, overly competitive, overly introverted, and overly expressive (no significant differences in the scales for overly cold, overly subassertive/subservient, overly exploitable/compliant, and overly nurturant/friendly). Weight loss was additionally observed (p < 0.001). Topiramate appears to be a safe and effective agent in the treatment in women with borderline personality disorder. Additional weight loss can be expected.

A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder.

Abstract: In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores or =50% reduction). Remission (MADRS score < or =12) was achieved by 51% of patients with citalopram and 53% with placebo. A post hoc analysis revealed that more than two thirds of all patients received psychotherapy during this study. For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively). Mild to moderate treatment-emergent adverse events were reported in 75% citalopram and 71% of placebo patients, most commonly headache, nausea, and insomnia. Serious adverse events occurred in 14% to 15% in both groups. Suicide attempts, including suicidal thoughts and tendencies, were reported by 5 patients in the placebo group and by 14 patients in the citalopram group (not significant) with no pattern with respect to duration of treatment, time of onset, or dosage. In contrast, the suicidal ideation (Kiddie-SADS-P) single item showed worsening more frequently in the placebo (18%) than in the citalopram group (8%).

Sertraline treatment of co-occurring alcohol dependence and major depression.

Abstract: Background:Major depressive disorder occurs commonly in association with alcohol dependence, both in clinical samples and in the community. Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results. This multicenter, double-blind, placebo-controlled tri

A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability.

Abstract: In this double-blind, multicenter study, bupropion XL, a norepinephrine-dopamine reuptake inhibitor, and venlafaxine XR, a serotonin-norepinephrine reuptake inhibitor, were compared with regard to sexual functioning, efficacy, and tolerability. A total of 348 sexually active adult outpatients with depression were randomized to receive bupropion XL (titrated to a target dose of 300-450 mg/d) or venlafaxine XR (titrated to a target dose of 150-225 mg/d) for 12 weeks. Total scores on the primary dependent variable, the Changes in Sexual Functioning Questionnaire (self-report), increased for subjects receiving bupropion XL and decreased for those treated with venlafaxine XR; the mean change scores differed significantly between groups from week 2 onward. Among subjects with normal pretreatment sexual functioning, Changes in Sexual Functioning Questionnaire total scores remained essentially unchanged for the bupropion XL group but were decreased significantly for the venlafaxine XR group; mean change scores also differed between groups from week 2 onward. Although the therapies resulted in similar change on the 17-item Hamilton Depression Rating Scale, remission rates were significantly higher among those treated with bupropion XL (46%) versus venlafaxine XR (33%) (odds ratio, 1.93; 95% confidence interval, 1.07-3.46). Aside from adverse effects of venlafaxine XR on sexual function, both treatments were reasonably well tolerated. In conclusion, in this patient population (ie, relatively young, sexually active outpatients), bupropion XL was at least as effective as venlafaxine XR and had a significantly more favorable sexual side effect profile.

Gamma-hydroxybutyrate and ethanol effects and interactions in humans.

Abstract: Gamma-hydroxybutyrate (GHB) has become a common drug of abuse in the United States and Europe in recent years. GHB was used in the late 1980s by body builders as a nonanabolic steroid performance enhancer and became widely available for sale in health food stores, gymnasiums, and via the Internet. Later, as the reputation for its euphoric effects grew, GHB became popular as a drug of abuse at dance clubs and "rave" parties. More recently, GHB has been used as a drug to facilitate sexual assault. Because of its abuse potential, GHB was classified as a Schedule I controlled substance in 2000, with dual scheduling instituted 2 years later when GHB became Food and Drug Administration approved as the pharmaceutical product Xyrem. In recent years, GHB has been a major cause of emergency department visits for drug-induced central nervous system depression.1–5 In overdose, GHB produces coma, often associated with hypothermia, bradycardia, hypotonia, myoclonus, and seizure-like activity.1,2 In very high doses, respiratory depression and death can occur.3–5 At lower doses, the primary effects of GHB are drowsiness, alcohol-like inebriation, dizziness, and induction of sleep.6,7 Gamma-hydroxybutyrate was previously studied as an anesthetic agent, and has also been studied as a medication for the treatment of cataplexy, a symptom of narcolepsy. Some effectiveness for this indication has been demonstrated, and GHB is currently Food and Drug Administration approved for use as a Schedule III drug for the treatment of narcolepsy.8 In addition, GHB has been marketed in Italy for the treatment of alcoholism since 1994. Psychomotor performance has been studied in healthy volunteers receiving GHB 12.5 and 25 mg/kg, and no significant effects of GHB were observed.6 Gamma-hydroxybutyrate is found naturally in the human body as a degradation product of the neurotransmitter, gamma-aminobutyric acid. GHB is extensively metabolized, in part to succinic acid, then through the tricarboxylic acid pathway, and in part by beta oxidation.9,10 Alcohol dehydrogenase has been postulated to contribute to GHB metabolism in animal and human liver.11 There is evidence of dose-dependent metabolism. The disposition kinetics of GHB in humans have been described in 3 published studies using doses of 12.5 to 50 mg/kg orally.12–14 The average elimination half-life after single doses ranged from 30 to 50 minutes, and the time to peak concentration averaged 30 to 40 minutes, consistent with rapid gastrointestinal absorption. In recreational use, GHB is frequently ingested with other drugs, including most commonly ethanol, which has sedative effects similar to those of GHB. There is a concern that these drugs may interact synergistically in producing sedation. However, this has not been well studied in doses of GHB that are relevant to therapeutic dosing or to recreational use. One study of the combination of GHB and low-dose ethanol showed significant impairment of reaction time with the combination.15 There have been no human studies conducted on the pharmacokinetic interactions between GHB and ethanol. We examined the effects of ethanol on the pharmacokinetics of GHB, and the pharmacodynamic interactions between ethanol and GHB in healthy human volunteers. We used a 50-mg/kg dose of GHB, which is comparable to doses used in the treatment of narcolepsy. We administered 0.6-g/kg dose of ethanol, which was projected to produce blood alcohol concentrations of about 50 mg/dL. Our objectives were to (1) identify any significant pharmacokinetic interactions that exist between these 2 sedative-hypnotic drugs; (2) determine if coingestion of ethanol and GHB produces greater cognitive, hemodynamic, and subjective mood effects than either GHB or ethanol alone; and (3) explore differences in response to GHB and ethanol between men and women, and people of different races. In this article, we report our findings on the pharmacokinetics and the hemodynamic effects of GHB and ethanol. Subjective drug effects, effects of race and sex, and cognitive testing will be reported separately.

A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms.

Abstract: Objective: The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms. Methods: This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF). Results: At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For up to 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). Over 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs. 29.7%; P = 0.003) and remained longer on medication (median, 163 vs. 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbAlc, and weight. Conclusions: Over 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.

The effects of sertraline on severe tinnitus suffering--a randomized, double-blind, placebo-controlled study.

Abstract: Objective:The relationship between tinnitus and anxiety and depressive disorders has been frequently alluded to, but there are few studies on antidepressants in the treatment of tinnitus, and the efficacy of sertraline on severe refractory tinnitus has not been reported.Method:Consecutive tinnitus p

Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin and dopamine transporter and receptor polymorphisms.

Abstract: Spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) have been developed as a result of the thalidomide disaster, whereby thousands of children world-wide were born with birth defects. The Swedish Adverse Drug Reactions Advisory Committee was established in 1965. Since 1975, reporting has been compulsory for all suspected serious or new ADRs. International collaboration started in 1968 with countries contributing their ADR reports to an international database set up by the World Health Organization. ADRs represent the negative side of the benefit-to-risk balance that in theory needs to be counteracted by perceived or established positive drug effects. All drugs are subject to preclinical and clinical testing prior to marketing authorization. However, these studies are insufficient to detect rare ADRs, ADRs that occur after long-term administration or with latency, ADRs that occur in special patient groups such as children, the elderly, patients with renal or hepatic insufficiency or patients on concomitant drug treatment, and ADRs that represent a modest increase in the risk of diseases (including mortality) that are prevalent in the study population. Postmarketing surveillance of drugs is therefore essential, and regulatory action may be needed on the basis of new ADR information. SRSs are important sources of ADR information as exemplified here by the evaluation of peripheral sensory disturbances with fluoroquinolones, hyponatremia with antidepressants, blood dyscrasias with dipyrone, glucose intolerance with atypical antipsychotics, pulmonary embolism with combined oral contraceptives and extrapyramidal symptoms with selective serotonin reuptake inhibitors. SRSs can be used to study clinical manifestations of ADRs (that can give insights into potential ADR mechanisms), risk factors for the ADR or for specific outcomes of the ADR, and ADR reporting incidences when combined with sales data. Signals from SRSs may need to be studied further e.g., by use of large-scale epidemiologic studies based on record linkage between drug prescription databases and health databases. Owing to the rapid availability of information, however, SRSs are likely to remain of major importance for the post-marketing surveillance of drugs.

Selegiline transdermal system in the prevention of relapse of major depressive disorder: a 52-week, double-blind, placebo-substitution, parallel-group clinical trial.

Abstract: The selegiline transdermal system (STS) is a monoamine oxidase inhibitor (MAOI) with unique pharmacokinetic and pharmacodynamic properties that was developed to overcome limitations of orally administered MAOIs, particularly dietary tyramine restrictions We present data from a long-term study assessing the safety and efficacy of initial and continuation STS therapy in patients with major depressive disorder (MDD) After 10 weeks of treatment with STS 6 mg/24 h, 322 patients who responded with a 17-item Hamilton Depression Rating Scale score of 10 or less were randomly assigned to double-blind treatment with STS 6 mg/24 h or placebo for 52 weeks Relapse was defined as meeting the following criteria on 2 consecutive visits: (1) 17-item Hamilton Depression Rating Scale score of 14 or more, (2) a Clinical Global Impression of Severity score of 3 or more with a 2-point increase from double-blind baseline, and (3) the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode At study week 52, significantly fewer STS patients experienced relapse of major depressive episode (25/149 [168%]) compared with placebo (50/163 [307%]) (P = 00025) In addition, patients receiving STS experienced a significantly longer time to relapse compared with those receiving placebo (P = 00048) The safety profile of STS was similar to placebo, with the exception of application-site reactions (STS, 152%; placebo, 37%) No cases of hypertensive crisis were reported, despite the lack of requirement for dietary tyramine restrictions In conclusion, STS was well tolerated and efficacious in maintaining a sustained response in MDD patients The results of this study suggest that STS may be suitable in the long-term treatment of MDD

The efficacy of olanzapine for decreasing cue-elicited craving in individuals with schizophrenia and cocaine dependence: a preliminary report.

Abstract: Objective: Although a growing body of research suggests that atypical neuroleptic medications are efficacious in the treatment of cocaine addiction among individuals with schizophrenia, more rigorously controlled trials are needed. To extend this research, we performed a 6-week double-blind study comparing olanzapine to haloperidol with the primary objective of reducing cue-elicited cocaine craving and the secondary aims of decreasing substance use, improving psychiatric symptoms, and determining an effect size for future studies. Methods: Thirty-one subjects with cocaine dependence and schizophrenia were randomized to olanzapine or haloperidol, underwent a cue-exposure procedure, and completed psychiatric and substance abuse ratings. Results: Individuals in the olanzapine group who completed the study had a significant reduction on the energy subscale of the Voris Cocaine Craving Scale at study completion compared with individuals in the haloperidol group. The olanzapine-treated group also had lower, but not statistically significant, PANSS General Psychopathology Subscale scores and fewer positive urine toxicology screens compared with those in the haloperidol group. Conclusion: This small, but rigorously controlled, pilot trial provides additional evidence for the use of atypical antipsychotics for the treatment of individuals with co-occurring schizophrenia and cocaine dependence. Reductions in craving were associated with medium to large effect sizes.

Interactions on mixing diazepam with methadone or buprenorphine in maintenance patients.

Abstract: Benzodiazepine use by patients in methadone and buprenorphine substitution treatment is common, despite safety concerns regarding these drug interactions. The relative safety of diazepam use by methadone- or buprenorphine-treated patients has not been systematically examined. This study aimed to examine the effect of single diazepam doses, within normal therapeutic range (doses: 0, 10, and 20 mg), upon physiological, subjective, and performance measures in stable methadone and buprenorphine-treated patients. In a double-blind, randomized crossover design, methadone- or buprenorphine-treated patients were administered their normal opioid dose and either placebo, 10-, or 20-mg diazepam, in balanced order over 3 sessions. Eight methadone- and 8 buprenorphine-prescribed patients with no concurrent benzodiazepine dependence or significant comorbidity were recruited from an outpatient addiction clinic in London. Measures were taken at baseline and for 6 hours after dosing, and included physiological responses (pulse rate, blood pressure, pupil size, respiratory rate, and peripheral pO2), subjective drug effects (Addiction Research Center Inventory subscales, visual analog scales of strength of drug effect, drug-liking, and sedation), and performance measures (simple reaction time, cancellation task, digit symbol substitution task, and balance). The 10- and 20-mg diazepam doses resulted in comparable subjective experiences of greater sedation and strength of drug effects in both patient groups, and had minimal impact on physiological parameters. However, diazepam had greater peak effects on performance measures (simple reaction time, digit symbol substitution task, and cancellation time) in methadone-treated than in buprenorphine-treated patients. Diazepam may significantly alter the response to opioid substitution treatment with methadone or buprenorphine.

Quality of life assessment in adult patients with attention-deficit/hyperactivity disorder treated with atomoxetine.

Abstract: Background:Attention-deficit/hyperactivity disorder (ADHD) has its onset during childhood and is estimated to affect 3% to 7% of school-aged children. Unfortunately, the disorder frequently persists into adult life. The burden of this disorder is considerable and is often characterized by academic (

Trends in the Adoption of Medications for Alcohol Dependence

Abstract: Increasing attention is being paid to the development and dissemination of effective pharmacotherapies for the treatment of alcohol and other drug dependence. However, numerous structural and philosophical barriers impede the widespread adoption of these treatment approaches in everyday clinical practice. Research is needed to understand and overcome this gap. Drawing upon data collected from 2 large samples of substance abuse treatment providers at multiple time points, this article examines the prevalence and correlates of the adoption of the currently available pharmacotherapies for alcohol dependence: disulfiram, oral naltrexone, and acamprosate. These data suggest that the proportion of treatment programs using pharmacotherapies for alcohol dependence has been declining over time. In addition, the proportion of patients to whom these medications are prescribed is notably low. The adoption of disulfiram and naltrexone is significantly more likely in programs that are accredited, employ at least 1 physician, offer integrated care for patients with co-occurring psychiatric conditions, derive proportionately more revenue from commercial insurance payers, and have fewer linkages with the criminal justice system. Preliminary data suggest that the early adoption of acamprosate is following a similar pattern. Recommendations for addressing challenges to the diffusion of pharmacotherapies for alcohol dependence are presented.

The early effect of olanzapine and risperidone on insulin secretion in atypical-naïve schizophrenic patients.

Abstract: Recently, increasing attention has been drawn to the potential diabetogenic effect of atypical antipsychotics. The goal of this prospective study is to evaluate the early effect of olanzapine and risperidone treatment on pancreatic beta-cell function in atypical-naive schizophrenic patients. Twenty-six subjects were assigned randomly to therapy with olanzapine or risperidone for 14 days. The metabolic parameters were quantitatively assessed by using the intravenous glucose tolerance test. The levels of fasting glucose, fasting insulin, lipid profiles, and leptin were also assessed. There were no significant within-group changes in weight or body mass index for both groups after 2 weeks of treatment. The levels of fasting glucose, fasting insulin, cholesterol, or leptin did not change in both groups. The triglyceride level significantly increased in olanzapine group. Glucose disappearance rate and insulin sensitivity did not change in both groups. Insulin secretion significantly decreased in olanzapine group. After 2 weeks of olanzapine treatment, schizophrenic patients decreased insulin secretory response to a hyperglycemic challenge. The results of this study support the hypothesis that olanzapine might directly impair pancreatic beta-cell function.

Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial.

Abstract: Background: Dehydroepiandrosterone (DHEA) augmentation has been reported, in a preliminary fashion, to be useful in the management of schizophrenia symptoms and side effects. In this study, the intention was to investigate the efficacy and safety of DHEA administration to ongoing antipsychotic medication in a multicenter, 12-week, double-blind, randomized, placebo-controlled, crossover trial. Methods: Fifty-five of 62 inpatients and outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia completed the trial. Patients were randomly allocated to 2 treatment groups receiving either DHEA (200 mg/d) or placebo for 6 weeks with the crossover between DHEA and placebo occurring after 6 weeks. Patients continued to receive their regular antipsychotic medication for the duration of the study. Results: Compared with placebo, DHEA administration did not produce significant improvement in clinical symptoms, side effects, and quality-of-life scores. However, 6 weeks of DHEA administration (but not placebo) was associated with a significant improvement in Positive and Negative Symptom Scale ratings compared with baseline. Furthermore, 6 weeks of DHEA treatment was associated with significant improvement in cognitive functions of visual sustained attention and visual and movement skills compared with placebo conditions. The DHEA augmentation was associated with elevations of serum concentrations of both DHEA and its sulfate ester. The DHEA treatment was well tolerated without any serious adverse effects. Conclusion: This short-term study does not support DHEA's value as an effective adjunct in the treatment of symptoms, side effects, and quality-of-life impairment in schizophrenia, while suggesting that DHEA improves sustained attention and visual and movement skills. A long-term, large-scale study with a broader dose range is warranted to further investigate DHEA's role in the management of schizophrenia.

Nontricyclic antidepressants - Predictors of nonadherence

Abstract: Second-generation antipsychotics (SGAs) have generally replaced classic neuroleptics in managing bipolar disorder because of their property of inducing extrapyramidal symptoms (EPS) less frequently than conventional agents. However, EPS and tardive dyskinesia both remain a concern especially in bipolar patients who may be at greater risk of developing these unwanted events. Hence, the aim of this study was to identify a definite rank order of EPS potential among such agents. All original research articles published in English on the use of SGAs for the treatment of bipolar patients were identified through a comprehensive Medline search. Only double-blind, randomized, placebo- and/or active comparator-controlled studies evaluating the effectiveness of atypical antipsychotics in bipolar patients were included in this article. Available literature data seem to suggest that EPS may occur in a significantly greater proportion of aripiprazole-treated patients than placebo-treated patients. The relevant bias characterizing most of quetiapine trials makes the finding that the incidence of EPS does not differ statistically between medicated and placebo groups doubtful. Among SGAs, risperidone seems to be associated with the highest risk of inducing EPS at doses lower than 6 mg/d. Conversely, data on olanzapine appear to be quite reassuring. Although it has been reported that there are no statistically significant differences between ziprasidone- and placebo-treated patients in the incidence rates of EPS, this information requires further confirmation. Thus, as it regards the risk of inducing EPS, among SGAs, olanzapine should be considered a first-choice medication for bipolar patients. However, clinicians should take into consideration the relatively high risk of metabolic complications associated with olanzapine use as well as with most of the other SGAs.

One-year mortality rates of patients receiving methadone and buprenorphine maintenance therapy: a nationally representative cohort study in 2694 patients.

Abstract: Mortality rates in drug-dependent patients in substitution treatment remain a matter of debate. Although several retrospective toxicological or forensic postmortem studies on this issue have been conducted, few prospective studies have addressed this problem. In a nationally representative sample of 2694 opioid dependent patients in substitution treatment either with methadone or buprenorphine at baseline were monitored over a 12-month period (response rate, 91%). A total number of 1629 (60.4%) were still in treatment after 12 months. The overall mortality rate was 1.04%. In total, 28 patients of the initial sample deceased within the 1-year follow-up period. Eleven (0.4%) of these deaths are due to a fatal intoxication. Three patients (0.1%) died of human immunodeficiency virus/acquired immunodeficiency syndrome, and 3 (0.1%) committed suicide. Thirteen of these patients (4 with overdose/polyintoxication) were not in substitution treatment at the time of death. Other reasons included accidents and deaths due to other medical conditions. Only in one case the reason could not be ascertained. The mortality rate was similar in methadone as compared with buprenorphine patients. Taking into account the high comorbidity of opioid dependent patients and the severity of dependence, the mortality rate of approximately 1% confirms that maintenance treatment could be regarded as a fairly safe treatment.

Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning.

Abstract: This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.

Efficacy of topiramate, valproate, and their combination on aggression/agitation behavior in patients with psychosis.

Abstract: :Topiramate is an antiepileptic drug, recently also used in the treatment of psychiatric diseases. Inasmuch as topiramate and valproate, which are currently used for aggressive behavior, share several pharmacological mechanisms (positive modulatory effect on the GABA activity and negative mo