Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression.

The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind, placebo-substitution, continuation treatment trial. After 16 weeks of acute, single-blind treatment with nefazodone, 131 patients responding to treatment and in stable remission were randomized in a 36-week double-blind trial to either nefazodone (n = 65) or placebo (n = 66). Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy. Relapse rates were significantly lower for patients randomized to continued nefazodone treatment than for patients switched to placebo. Kaplan-Meier estimates of relapse rates 9 months (36 weeks) after the end of acute treatment were 1.8% for nefazodone versus 18.3% for placebo (P = 0.009) by the Hamilton Depression Scale and 17.3% versus 32.8% (P = 0.028) by discontinuation for lack of efficacy. The mean modal dose of nefazodone was 412 mg/day at study endpoint. These results demonstrate the clinical effectiveness of up to 1 year's treatment (16 weeks acute and 36 weeks continuation) with nefazodone in depressed patients. Long-term efficacy of nefazodone was accompanied by a good safety profile without any weight gain and with minimal symptoms of withdrawal upon abrupt discontinuation of treatment.

A double-blind trial of low- and high-dose ranges of gepirone-ER compared with placebo in the treatment of depressed outpatients.

We report the results of a double-blind study comparing the efficacy and safety of low-dose (10-50 mg) and high-dose (20-100 mg) ranges of gepirone-extended release (ER) and placebo in 145 outpatients with major depressive disorder. At multiple time points and endpoint (Week 6), statistically significant reductions in Hamilton Rating Scale for Depression (HAM-D) scores were recorded for high-dose gepirone-ER compared to placebo. Analysis of the 17-item HAM-D and 28-item HAM-D scores indicated a relatively early onset of antidepressant efficacy with statistically significant results at treatment Weeks 1, 2, 4, and 6. A rapid response was evident in the high-dose group, beginning at Week 1 (p < .05). The most frequently reported adverse experiences were headache, nausea, dizziness, and insomnia. The results indicate that gepirone-ER is clearly superior to placebo in terms of antidepressant efficacy. When used at higher doses, gepirone-ER appears to be efficacious, safe, and well-tolerated in depressed out-patients.

Comparison of the effects on pupil size and accommodation of three regimens of topical dapiprazole.

BACKGROUND: Patients who have their pupils dilated for an eye examination traditionally have to wait several hours before their pupils return to normal size and their blurred vision (caused by paralysis of accommodation) resolves. Earlier studies with dapiprazole have demonstrated an accelerated reversal of dilatation. METHODS: Three regimens of dapiprazole were studied to determine the effects on pupil diameter and accommodation after mydriasis produced by 2.5% phenylephrine and 0.5% tropicamide. Test regimens included one drop and 1 + 1 drop regimens, compared with a 2 + 2 drop reference regimen. Dapiprazole was administered in one eye and placebo in the other. Mean change from baseline was analysed for pupil diameter and accommodation at various time points after drug administration. Also, for the same variables, 90% confidence intervals for the areas under the curve (AUC) were computed. RESULTS: Both test regimens were equivalent to the reference regimen on the basis of mean change from baseline for pupil diameter and accommodation at individual time points, and for the mean AUC. Most signs and symptoms (injection, stinging, burning, lid oedema, and ptosis) were less frequent in the test regimen treated eyes. There was no significant interaction between regimen and eye colour. CONCLUSION: This study indicates that a lower dosage (for example, one drop) is also efficacious and has the added benefit of fewer side effects.

A fixed-dose study of adinazolam-SR tablets in generalized anxiety disorder.

1. This four-week, randomized, double-blind, multicenter study compared the efficacy and safety of adinazolam-SR, at three dosage levels, with placebo. Forty (40) patients were randomized at our site: 10 to adinazolam 30 mg/day, 10 to 60 mg/day, 10 to 90 mg/day, and 10 to placebo. All patients were moderately anxious with Hamilton Anxiety Scale (HAM-A) scores of > or = 21 at baseline. 2. The data were analyzed by pooling the three adinazolam groups and comparing them with the placebo group using t-tests. HAM-A scores decreased significantly more in the pooled adinazolam-SR treatment group than in the placebo group at both Week one (p < .02) and at Week two (p < .01), as well as at endpoint (p < .03). 3. At endpoint the adinazolam-treated group included 8 "responders" (> or = 50% reduction on the baseline HAM-A score) while none of the placebo patients were responders (p < .05). Dose-response effects were evaluated and relationships were not statistically significant. 4. The results indicate that adinazolam-SR was clearly superior to placebo for the treatment of patients suffering from Generalized Anxiety Disorder.

Are selective serotonin reuptake inhibitors well tolerated in somatizing depressives?

This retrospective evaluation included 89 patients who participated in two independent clinical investigations of the antidepressant medications paroxetine and fluoxetine. Baseline gastrointestinal (GI) somatic symptoms, as indicated by the baseline scores on the Hamilton Rating Scale for Depression (HAM-D) items 11, 12, and 16, the Symptom Checklist (SCL) items 19 and 40, and the Covi Anxiety Scale somatic anxiety item were analyzed for their discriminative ability in predicting which patients would subsequently develop adverse GI side effects on medication. Subjects with baseline complaints of nausea or upset stomach (SCL #40), GI somatic symptoms (HAM-D #11 and #12, Covi somatic anxiety), or weight loss (HAM-D #16) were not statistically more likely to develop GI side effects on paroxetine or fluoxetine. Only a baseline complaint of appetite loss (SCL #19) was associated with subsequent GI side effects on paroxetine to a statistically significant degree (p < .05).

Predictors of placebo response: a retrospective analysis.

This retrospective evaluation involved 197 patients from independent clinical investigations of four antidepressant medications. Six variables were analyzed for their discriminative utility in predicting placebo response rates: gender; marital status; age; education; duration of illness; and severity of depressive symptomatology, as measured by Hamilton Rating Scale for Depression (HAM-D or HDRS) scores. Men were slightly more responsive to placebo than were women (29.8%, n = 94 vs. 24.3%, n = 103). Married patients demonstrated the highest probability of a positive placebo response (38.15%, n = 76), as compared with widowed/separated/divorced (21.9%, n = 73) or single (16.7%, n = 48) patients. A trend toward an increased probability of placebo response was detected for patients aged 60 and above (35.7%, n = 14). Educational level achieved and duration of illness were not predictive. Severity of illness proved most noteworthy, with the placebo response rate higher in the more mild patients (40.8%, n = 27 vs. 23.4%, n = 77).

Anticholinergic agents for prophylaxis of neuroleptic-induced dystonic reactions: a prospective study.

The development of acute dystonic reactions was monitored in 202 acute psychiatric patients during initial hospitalization and treatment with various neuroleptic drugs in a prospective study. Data were analyzed to determine the effect of anticholinergic prophylaxis, age, sex, and type and dosage of neuroleptic on the incidence of dystonic reactions. Nearly 90% of dystonic reactions occurred by the third day of treatment. The overall trend favored the prophylactic use of antiparkinsonian drugs with all neuroleptics, and the effect of this prophylaxis with haloperidol was statistically significant. Because anticholinergic prophylaxis was used more often when larger dosages of neuroleptics were prescribed, an added effect in the observed trend for fewer dystonic reactions is suggested.

Hair analysis for detection of phencyclidine in newly admitted psychiatric patients.

The authors implemented a new procedure for analyzing phencyclidine (PCP) content in hair. They compare the results of analyses of hair with results of analyses of blood and urine in 47 patients newly hospitalized with acute psychiatric illness. Hair analysis identified 11 patients who had used PCP, and blood and urine analyses did not identify any among the sample population. In three patients, the results of hair analysis aided in establishing a diagnosis of PCP intoxication. The authors discuss interpretations of their findings and psychiatric applications of this new technique.

Self-mutilation of the eye.

While the act of self-enucleation is rare, other self-inflicted eye injuries may be more common. Six patients are reported who have documented histories of ocular self-mutilation. Several common factors are observed in these patients and in other cases reported in the literature: (1) the patient was judged to be psychotic; (2) the patient had a tyrannical conscience; (3) a source of guilt was present; (4) this guilt was displaced to the eye; and (5) an attempt at self-inflicted eye injury was followed by relief from anxiety when completed or by frustration when injury was prevented.

A review of psychoactive drug-involved deaths in nine major United States cities.

Detailed psychosocial and biomedical data were collected in 2,000 psychoactive drug-involved deaths occurring from 1972 through 1974 in nine large cities in the United States. The cases were selected representatively by the medical examiners or coroners in each city. Also, proficiency studies were carried out of the toxicological laboratories associated with these nine cooperating data collection centers. There were striking intercity psychosocial and biomedical differences in these psychoactive drug-involved deaths. These differences were based not simply in demographic regional population differences but also on the kinds of psychoactive drugs used as well as the role of the drug in contributing to death and whether the death was a result of an accident, suicide, homicide, or unknown intent. Also, a lack of uniformity was demonstrated in the quality control of the toxicological laboratories associated with the offices of these nine medical examiners or coroners, which suggests varying degrees of accuracy in resulting medicolegal diagnoses. Hence national programs of drug abuse deterrence or prevention and treatment should deal specifically with the variety of psychoactive drug-involved deaths occurring in different urban areas rather than approaching these problems globally as if they were uniform and homogeneous, and our toxicological proficiency studies accentuate the importance of mandatory quality control studies for all toxicological laboratories in the United States.

The tricyclic antidepressants.

Because only 9.4% of depressions are recognized at initial evaluation by primary physicians, the diagnosis of depression is important. Forty percent of a group of mixed depressions will resolve in a month without treatment, and 70% will resolve with the use of tricyclic antidepressants. Research on plasma levels of tricyclic antidepressants suggest new clinical strategies for adjusting dosages; neurochemical studies may provide an appropriate selection process for choosing a tricyclic antidepressant.