Robert J. Bielski

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 years 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 comparison of self-control therapy and combined self-control therapy and antidepressant medication in the treatment of depression.

This study examined the differential efficacy of self-control therapy alone and self-control therapy plus antidepressant medication in treating unipolar depression. Subjects participated in a 12-week self-control treatment program in which they were trained to identify and modify dysfunctional patterns of thought and behavior (i.e., biases in the areas of selective attention, standard setting, self-attribution, self-reinforcement, etc.). Half of the clinical cohort also received antidepressant medication. Thirty-two individuals were randomly assigned to one of four therapy groups which were generated from a 2×2 (therapist×treatment condition) design. No significant effects were detected for the therapist variable. Both treatment conditions evidenced marked decreases in depressive symptomatology. Combined treatment resulted in significantly more rapid improvement as measured by the Beck Depression Inventory. Three-month follow-up assessments indicate that treatment gains were maintained in both groups.

Effect of light therapy on salivary melatonin in seasonal affective disorder

To investigate the role of a light-induced advance in the timing of the melatonin rhythm in seasonal affective disorder, 11 depressed patients underwent 2 weeks of light therapy with full spectrum or cool white light. Evening saliva samples were collected before and after each week of treatment and assayed for melatonin to determine the time of onset of nocturnal secretion. Both treatments reduced depression scores, advanced the timing of the melatonin rhythm, and increased melatonin concentrations. Time of onset of the nocturnal increase in melatonin did not differ between clinical responders and nonresponders, suggesting that a phase advance in the onset of nocturnal melatonin secretion is not sufficient to induce clinical remission in seasonal affective disorder.

Efficacy of pregabalin in generalized social anxiety disorder: results of a double-blind, placebo-controlled, fixed-dose study.

The objective of this study was to evaluate the efficacy and tolerability of pregabalin for the treatment of generalized social anxiety disorder (SAD). Patients with generalized SAD, who met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria (total N=329), were randomly assigned to 11 weeks of double-blind treatment with fixed daily doses of either pregabalin (300, 450, and 600(mg) or placebo. The treatment with pregabalin (600(mg) was associated with a significantly greater mean reduction in the Liebowitz Social Anxiety Scale total score, from baseline to endpoint, compared with placebo (-29.8 vs. -19.7; P= 0.0099), whereas reduction on pregabalin (300(mg, -20.2) and pregabalin (450(mg, -25.5) was not significant Treatment with pregabalin (600(mg) was also associated with a significantly greater improvement than placebo on the fear and avoidance subscales of the Liebowitz Social Anxiety Scale, as well as the majority of other secondary measures. Onset of improvement occurred by week 1 in the pregabalin 600-mg dose group. The most common adverse events on all three doses of pregabalin were somnolence and dizziness. Consistent with a previous study, the results of this study suggest that the 600-mg dose of pregabalin per day may be efficacious in the treatment of SAD.

Urinary Mhpg Excretion and Treatment with Desipramine or Amitriptyline: Prediction of Response, Effect of Treatment, and Methodological Hazards

Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was measured in 49 unipolar depressed outpatients to examine the relationship between pretreatment MHPG levels and therapeutic response to desipramine and amitriptyline and to determine the effects of these agents on MHPG excretion. Pretreatment MHPG excretion was greater in amitriptyline responders than amitriptyline nonresponders, but no different in desipramine responders compared to desipramine nonresponders. Pretreatment MHPG excretion did not differentiate desipramine from amitriptyline responders. Treatment for 3 weeks was associated with a decrement in MHPG excertion, particularly in the desipramine responders and combined desipramine and amitriptyline responders. Among patients within the postulated optimal desipramine plasma level range and patients with plasma amitriptyline plus nortriptyline levels > 70 ng/ml, high pretment MHPG excretion predicted therapeutic response and response was accompanied by a reduction in MHPG excretion. The interpretation of these findings is possibly confouded by the demonstration of a poor correlation (r = 0.61) between duplicate MHPG samples analyzed by a widely employed gas chromatography method and a gas chromatography/mass spectrometry technique. The methodological pitfalls encountered in the course of this investigation and their possible implications for similar studies are discussed.

Phototherapy with broad spectrum white fluorescent light: a comparative study.

The principles of photobiology suggest that the antidepressant effect of phototherapy depends on the dose and spectrum of light. We investigated the effect of spectrum by comparing two broad spectrum fluorescent light sources with different spectral distributions. In a crossover design, 11 patients with seasonal affective disorder (SAD) were treated with broad spectrum fluorescent and cool white light for 7 days. Scores on the Hamilton Rating Scale for Depression were reduced from 22.5 to 8.1 with broad spectrum fluorescent light and from 23.5 to 8.8 with cool white light. The results suggest that both light sources are effective treatments.

Fracture of Lower Femoral Epiphysis in an Infant at Birth: A Rare Obstetrical Injury

We report a case of rare birth injury leading to physeal fracture after a routine cesarean delivery. Because plain radiographics are often normal, therefore these physeal fractures usually present a diagnostic challenge in the newborn. In this case, ultrasonography and magnetic resonance imaging were helpful in making an early accurate diagnosis. The infant received prompt treatment and the physeal fracture healed uneventfully. Physeal fractures should be included in the birth injuries following routine cesarean delivery.

Geometric analysis of coronal decompensation in idiopathic scoliosis

Study Design. Frontal plane geometry of postoperative curves was analyzed using a geometric model to investigate the relationship between coronal decompensation and postoperative apical shifts from the center sacral line for various thoracic and lumbar Cobb angles. Objective. To determine if a balanced spinal configuration is possible when the postoperative lumbar curve is larger than the thoracic curve, and to determine the limits on the postoperative magnitude of the lumbar curve relative to the thoracic curve beyond which a spinal configuration with acceptable balance cannot be achieved. Summary of Background Data. Previous studies have suggested that overcorrection of the primary thoracic curve may be the principal cause of coronal de‐compensation after selective thoracic correction and fusion in King Type II curves. Also, other causative factors, such as inappropriate selection of fusion levels and hook patterns, have been implicated as possible reasons for decompensation after Cotrel‐Dubousset instrumentation for idiopathic scoliosis. Methods. Postoperative thoracic curves of 20°, 25°, and 30° were simulated on a model spine. For each thoracic Cobb angle, three left lumbar curves were simulated with the lumbar curve larger than thoracic by 5°, 10°, and 15°. For each combination of thoracic and lumbar Cobb angles, spinal configurations corresponding to different lateral shifts of the thoracic and lumbar apical vertebrae from the center sacral line were obtained. Results. For a given combination of postoperative thoracic and lumbar Cobb angles, there is an optimal range of postoperative lateral distance between the thoracic and lumbar apices (relative apical distance) that will maintain acceptable balance (decompensation ≤ 10 mm). Smaller values of the relative apical distance will decompensate the spine. For a constant postoperative thoracic Cobb angle, the postoperative distance between the thoracic and lumbar apices needed to maintain a balanced spine increases with increasing postoperative lumbar Cobb angle. Similarly, for a constant difference between the postoperative thoracic and lumbar Cobb angles, the postoperative distance between the thoracic and lumbar apices needed to maintain a balance spine increases with increasing postoperative thoracic Cobb angle. For postoperative thoracic curves of 20°‐30°, acceptable balance can be achieved when the magnitude of the postoperative lumbar curve is up to twice the thoracic curve as long as adequate postoperative relative apical distance can be maintained. Conclusions. Decompensation does not appear to be caused by the relative magnitudes of the postoperative thoracic and lumbar curves, but is a result of inadequate relative distance between the thoracic and lumbar apical vertebrae in the postoperative geometry.

Intraosseous infusions: effects on the immature physis--an experimental model in rabbits.

Summary: Intraosseous infusions are becoming more popular in critical care and emergency room settings in pediatric patients. Spinal needles are introduced in metaphyseal bone to establish intravenous (i.v.) access when standard i.v. routes are not accessible. An experimental rabbit model was constructed to simulate intraosseous infusion in human infants to determine effects on the physis and growth rate of the infused bone. Twenty immature rabbits were infused with saline, bicarbonate, or dopamine solutions. Rabbits were killed and tibias harvested at 24 h and 3 weeks, and gross and histologic sections were examined. No growth disturbance occurred in any of the infused tibias. Gross and microscopic changes were confined to metaphyseal bone and had completely resolved after 3 weeks. There was no evidence of physeal injury.

Estazolam treatment of insomnia in generalized anxiety disorder : a placebo-controlled study

Estazolam, a triazolobenzodiazepine with an intermediate elimination half-life, has been shown previously to be an effective and safe hypnotic in insomniacs without concomitant psychiatric illness. Our study of the efficacy of estazolam in patients with insomnia associated with generalized anxiety disorder began when 108 patients meeting criteria for generalized anxiety disorder (mean total score of Hamilton Rating Scale for Anxiety [HAM-A] = 22.0 ± 3.1 [SD]) and insomnia were given single-blind placebo for 7 nights. Nine patients whose anxiety and/or insomnia improved were dropped as placebo responders. The remaining 99 patients were randomly allocated (1:1) to double-blind treatment with either estazolam 2.0 mg or matching placebo for 7 nights. Hypnotic efficacy, as determined by patient-completed sleep questionnaires, was statistically significant for estazolam 2.0 mg versus placebo for all sleep indices (p <0.01). Patients treated with estazolam 2.0 mg showed significantly greater improvement in anxiety than those receiving placebo on the mean total score of HAM-A ([placebo, −3.4; estazolam, −7.1; p <0.001] and without the insomnia item [placebo, −2.7; estazolam, −5.5; p<0.001]). Anxiety scores on the State-Trait Anxiety Inventory showed greater improvement in the estazolam group, but without statistical significance (p = 0.237). Estazolam 2.0 mg is an effective hypnotic in patients with generalized anxiety disorder and appears to have a favorable anxiolytic action.