Valerian as a hypnotic for Hispanic patients.

Valerian is a botanical used for its sedative effects whose central nervous system activity is ascribed to multiple constituents. Twenty-three established outpatient symptomatic Hispanic volunteers receiving mental health services at a large urban hospital participated in this case study. All complained of insufficient sleep. They were asked to try a popular national brand of valerian ("Nature's Way", 470 mg valerian root) and completed sleep questionnaires at baseline and at the end of Weeks 1 and 2. They were instructed to take 1 capsule each night before retiring and were allowed to increase their dose to a maximum of 3 capsules after Week 1. Twenty patients completed the trial. On an ordinal scale of 1 (no effect), 3 (moderately helpful), and 5 (extremely helpful), 16 patients rated their insomnia as at least "moderately improved" at the end of Week 1. By Week 2, 16 still rated themselves at least "moderately improved," but 15 of them now described their response as either a 4 or a 5. Global improvement at Week 2 was significantly better than at Week 1 (Wilcoxon ranks test p = .005), perhaps reflecting a time-dependent or dose-response relationship. This case study suggests that valerian can be a supplement for improving insomnia in a symptomatic population.

Demographics, Prevalence, and Clinical Features of the Schizo-obsessive Subtype of Schizophrenia.

The schizo-obsessive subtype of schizophrenia has been proposed to describe the condition of patients with chronic psychotic disorders and prominent obsessive-compulsive (OC) symptoms. These patients differ from others with schizophrenia not only in their psychopathology, but perhaps also in their prognosis and pharmacotherapeutic response. Potent serotonin reuptake blockers, such as clomipramine, fluvoxamine, and fluoxetine, in conjunction with antipsychotics, can prove helpful in improving these patients' OC symptoms. The current study to access the demographics, prevalence, and clinical features of the schizo-obsessive subtype included established outpatients with a principal diagnosis of schizophrenia or schizoaffective disorder treated at a large urban public hospital. More than 50% of the hospital's psychiatric population is Hispanic. The Modified Maudsley Obsessive Compulsive Inventory (MMOCI) was used to identify prominent compulsive symptoms. Of the 52 patients who fulfilled the specific screening criteria, 17 (33%) also had prominent OC symptoms. Surprisingly, there was a statistical trend (P=0.06) for Hispanic patients to meet our threshold for the schizo-obsessive subtype. The MMOCI proved to be an adequate and efficient self-rated screening tool. The prevalence of the schizo-obsessive subtype, especially among Hispanic patients, highlights the importance for mental health professionals working with this population to identify and appropriately treat this group of patients.

Bupropion slow-release response in depression: diagnosis and biochemistry.

BACKGROUND: Bupropion has been previously shown to be particularly beneficial in bipolar and atypical depression. Previous research has supported a possible association of response to plasma levels and to changes in plasma homovanillic acid (HVA). These findings were here extended to bupropion slow-release (SR), a formulation with slower release kinetics. METHODS: Forty-one patients with major depressive disorder (DSM-III-R) completed 8 weeks of a fixed dose of 300 mg/day in two doses/day. Clinical outcome measures were the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). Biological parameters included plasma HVA and 3-methoxy-4-hydroxyphenyl-glycol (MHPG), as well as a final measurement of plasma bupropion and its metabolites. RESULTS: Response to bupropion SR differed among the three groups: results for change in HDRS and in BDI were greater in the bipolar and atypical than in the "typical" depressed patients. Mean change in HDRS was, respectively, of 15.6, 17.1, and 7.6 (F = 5.57, p < .01); mean change in the BDI, 21.1, 16.9, and 7.3 (F = 3.32, p < .05). Threobupropion levels correlated with HDRS scores (r = .47, p = .02, n = 23); plasma HVA and MHPG increased significantly (t = 2.31, p = .03; t = 2.15, p = .04, n = 17). Bipolar depressed patients' improvement in HDRS was related to increases in MHPG (r = .87, p = .01) and in HVA (r = .70, p = .08). CONCLUSIONS: This fixed-dose study indicates that there may be specific benefits for bupropion SR in atypical and bipolar depression, and that these benefits may be related also to plasma levels and biochemical changes in catecholamines. Due to the small sample size, replication is of key importance.

A double-blind study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation.

STUDY OBJECTIVE: To compare the utility of intramuscular lorazepam (LZ) with the combination of intramuscular haloperidol (HDL) and LZ to control acutely agitated behavior. DESIGN: Randomized double-blind comparison. SETTING: Psychiatric emergency service of a large, university-affiliated, municipal hospital. PATIENTS: Twenty subjects treated on the psychiatric emergency service. INTERVENTIONS: Patients received an injection of either LZ 2 mg (11 patients) or HDL 5 mg plus LZ 2 mg (9 patients). The Overt Aggression Scale (OAS), visual analog scales reflecting agitation and hostility, and the Clinical Global Impressions (CGI) severity scale were administered at baseline and 30, 60, 120, and 180 minutes after the injection. MEASUREMENTS AND MAIN RESULTS: Planned data comparisons included categoric assignment of patients as improved, as defined by decreases in outcome measures 60 minutes after the injection, as well as continuous variables up to 180 minutes after the injection. A significantly greater percentage of subjects receiving combined treatment improved on the specific measures 60 minutes after dosing (p<0.05). Kaplan-Meier survival analyses showed significant between-group differences in survival curves plotted for the entire study period (p<0.05). Repeated measures analyses of variance studying group differences showed that both groups improved over time, but between-group differences were not significant. The powers of these analyses were low due to the small sample. No serious adverse effects occurred in either treatment group. CONCLUSION: Our results suggest superior efficacy for HDL-LZ over LZ alone. Categoric tests of improvement at 60 minutes provided the strongest evidence of group differences.

Are fluoxetine plasma levels related to outcome in obsessive-compulsive disorder?

OBJECTIVE: In obsessive-compulsive disorder, the relationship between blood levels of serotonin reuptake inhibitors and clinical outcome is unclear. In a multicenter trial, the authors examined the relationship between steady state plasma levels of fluoxetine and norfluoxetine (determined after 7 weeks of treatment), and their sum, and clinical outcome. METHOD: Ratings of symptom severity of obsessive-compulsive disorder (Yale-Brown Obsessive Compulsive Scale scores) were obtained at baseline and after 13 weeks for 200 adult outpatients with moderately severe obsessive-compulsive disorder treated with fluoxetine doses of 20 mg/day (N = 68), 40 mg/day (N = 64), and 60 mg/day (N = 68). RESULTS: Mean plasma levels of fluoxetine and norfluoxetine were statistically significantly higher with higher dose. Statistical analyses revealed no significant relationship for plasma level of either molecule or their sum in predicting endpoint percent change in obsessive-compulsive scores. Plasma levels of patients with a marked response (decrease of 50% or more in obsessive-compulsive score) did not differ significantly from those of nonresponders (less than a 25% decrease in obsessive-compulsive score). No hint was seen of a therapeutic window or of a relationship limited to one gender or within the lowest dose group (20 mg/day). However, since S-norfluoxetine is a much more potent serotonin reuptake inhibitor than R-norfluoxetine, the absence of chiral (stereospecific) assays in this study limits the results. CONCLUSIONS: Steady state plasma levels of fluoxetine and norfluoxetine are not related to clinical outcome in patients with obsessive-compulsive disorder. Individual patients can be told only that the optimum dose of fluoxetine for them will be the dose that produces the largest therapeutic effect with the smallest side effect burden. Future studies should examine the predictive utility of measures of serotonergic neuronal function and, if plasma levels of norfluoxetine are examined, the use of chiral assays.

Lack of change in fluoxetine and norfluoxetine kinetics when switching from fluoxetine to paroxetine.

Pharmacokinetic interactions are possible with the prescription of two or more psychotropics. This caution could also apply to the proximal use of selective serotonin (5-hydroxytryptamine) reuptake inhibitors (SSRIs), especially those that may be potent inhibitors of specific hepatic metabolizing enzyme systems. Both fluoxetine (FLX) and paroxetine (PAR) are inhibitors of the cytochrome P4502D6 enzyme system. In order to assess the potential pharmacokinetic interactions between these two SSRIs, nine patients were first treated with fixed therapeutic doses of FLX for a minimum of 6 weeks. Subsequently, in a double-blind design, some of these patients were abruptly switched to PAR, 20 mg/day, and others were switched to placebo. Serum levels of FLX, norfluoxetine (NFLX), and PAR were collected before and at specific points after the switch. The results suggest that the clearance kinetics of FLX and NFLX are not affected by the abrupt switch to PAR. It was not possible to determine whether the kinetics of PAR were influenced by the residual FLX and NFLX concentrations.

Adverse events after the abrupt discontinuation of paroxetine.

Paroxetine is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. In contrast to other SSRIs, it has a relatively short half-life and lacks active metabolites. In three patients the abrupt discontinuation of paroxetine seemed associated with sudden and impairing effects. All three reported marked sleep disturbances and dizziness. They were prescribed the drug for a minimum of 10 weeks, and the maximum dosage was 40 mg/day. All patients experienced rapid remission of symptoms after paroxetine was reintroduced. We failed to observe similar reactions from the abrupt discontinuation at lower dosages. Gradual tapering of the agent for patients receiving more than 20 mg/day is recommended.

Management of treatment-refractory obsessive compulsive disorder patients.

Often obsessive compulsive disorder (OCD) patients are labeled as treatment refractory when some first-line options have not been fully explored. Most patients should be encouraged to participate in behavior therapy, even when pharmacotherapy alone has been partially successful. Antiobsessional agents such as clomipramine, fluoxetine, and fluvoxamine should be considered first-line drugs. Their prescription for a sufficient time and at therapeutic doses is imperative. Enhancement strategies for a selected group of OCD patients include low-dose high-potency neuroleptics. In addition, clonazepam can be helpful in augmenting the response to a first-line drug. Results from controlled studies with lithium and buspirone have been disappointing. If most of these pharmacologic alternatives fail, MAOIs appear to be the next best choice. Since in the future most referrals for treatment-refractory OCD patients will emanate from nonpsychiatrists, following a systemic strategy in their evaluation and pharmacologic management is most important.

Serotonergic antidepressants and their efficacy in obsessive compulsive disorder.

Since 1985, major advances have been made in the pharmacologic treatment of obsessive compulsive disorder. Clomipramine is undoubtedly effective. Other selective serotonin reuptake inhibitors, such as fluvoxamine and sertraline, seem effective as well. Fluoxetine's efficacy has been principally based on convincing open-label studies and clinical practice. No large controlled studies have been published. A preliminary analysis of a double-blind trial in which 51 obsessive compulsive disorder patients were randomly assigned to either placebo or three fixed doses of fluoxetine reveals that the drug is decisively helpful. Unexpectedly, the 20-mg/day dose was as effective as the 40- or 60-mg/day dose. Although these findings further advance our understanding of short-term pharmacologic treatments, few data are available regarding maintenance doses, relapse, and efficacy of adjunctive treatments.

Estazolam and flurazepam: a multicenter, placebo-controlled comparative study in outpatients with insomnia.

A multicenter, double-blind placebo-controlled clinical trial was designed to compare the safety and efficacy of estazolam compared with flurazepam as hypnotics. Outpatients complaining of insomnia were randomized to receive either estazolam 2 mg, flurazepam 30 mg or placebo for 7 consecutive nights. The analysis of efficacy was based on the patients' daily assessments of sleep and the investigators' global evaluations. Adverse events which were considered by the investigator to be attributable to, or of unknown relationship to the test medication were analyzed. The patient subjective questionnaire indicated that estazolam and flurazepam significantly improved all parameters (P less than .05) as compared to placebo. A marked or moderate improvement in sleep was reported by 81% (58/72), 78% (63/81) and 36% (27/76) of estazolam, flurazepam, and placebo recipients, respectively. There were no significant differences in hypnotic effect between estazolam and flurazepam. All efficacy parameters of the investigators' global evaluation improved significantly more (P less than .05) for patients receiving estazolam or flurazepam (except quality of sleep) than for those receiving placebo. The percentage of patients reporting any adverse experience was greatest for flurazepam (72%), followed by estazolam (59%), and placebo (43%). Somnolence and hypokinesia were the most commonly reported adverse events. An analysis of the global evaluation of side effects showed that flurazepam had a significantly worse side effect profile than estazolam (P less than .05) or placebo (P = .001). Estazolam and flurazepam effectively, and comparably, relieved insomnia when administered for 7 nights in adult patients complaining of insomnia. Estazolam demonstrated a more favorable side effect profile than flurazepam.

Comparative efficacy of estazolam, flurazepam, and placebo in outpatients with insomnia.

The efficacy and safety of estazolam, an investigational triazolobenzodiazepine, and flurazepam were compared in 65 insomniac outpatients. Patients completed sleep questionnaires each morning. Global evaluations demonstrated that both treatments were significantly superior to placebo. However, estazolam was preferred over flurazepam in a global rating that reflected how well rested and refreshed the subjects felt on arising. Improvement in complaints of difficulty in going to sleep showed only a trend toward significance favoring estazolam and flurazepam over placebo. Residual daytime drowsiness and fatigue accounted for approximately 70% of all side effects with both active treatments. Significantly more side effects occurred with flurazepam than with estazolam. Flurazepam-treated patients had a significantly more severe rating of adverse reactions than did placebo-treated patients.