Short-term augmentation of fluoxetine with clonazepam in the treatment of depression: a double-blind study.

OBJECTIVE: Because selective serotonin reuptake inhibitors (SSRIs) require 2-4 weeks to reach efficacy, the authors determined whether clonazepam augmentation of fluoxetine is superior to fluoxetine alone at the beginning of treatment for major depression. METHOD: Eighty adult outpatients with major depression who were rated as "moderately ill" or "markedly ill" on the Clinical Global Impression of Severity underwent 8 weeks of double-blind, randomized treatment with fluoxetine, 20 mg/day for all patients initially and 40 mg/day if needed after 6 weeks. One-half of these patients received clonazepam, 0.5 mg h.s. adjusted to two tablets by day 10 if needed, and the remainder received placebo, likewise adjusted. Clonazepam/placebo was gradually discontinued during days 21-33. Efficacy was evaluated by means of the Hamilton Depression Rating Scale, the Clinical Global Impression of Improvement, and a patient rating of global improvement. RESULTS: The patients taking clonazepam improved significantly more during the first 3 weeks of treatment according to ratings on the Hamilton scale (> or =50% improvement) and the clinician- and patient-rated global improvement measures ("much" or "very much" improved). Analysis of variance confirmed a significant effect of clonazepam for average Hamilton depression scores. No serious adverse events were found in either treatment group. Taper effects appeared modest and transitory. CONCLUSIONS: Clonazepam augmentation of fluoxetine was superior to fluoxetine alone in the first 3 weeks of treatment. This strategy may reduce suffering during early SSRI treatment, may partially suppress SSRI side effects, may increase compliance, and could possibly reduce the risk of suicide.

Short-term cotherapy with clonazepam and fluoxetine: anxiety, sleep disturbance and core symptoms of depression.

BACKGROUND: SSRIs resolve depression slowly and may increase anxiety or insomnia. Adding clonazepam to fluoxetine sped response, raising the question of mechanism of action: reducing symptoms co-existing with depression, suppressing side-effects, and/or alleviating core depressive symptoms. METHOD: Adult outpatients randomly assigned to double-blind treatment with fluoxetine 20 mg+placebo or fluoxetine+clonazepam 0.5-1.0 mg were assessed by a HAM-D anxiety cluster, sleep disturbance cluster, and core symptoms cluster. RESULTS: No serious AEs were noted; no cotherapy patients dropped for AEs. Cotherapy proved superior (HAM-D total, anxiety cluster, sleep disturbance cluster ANOVA P<0.001; core symptoms P<0.011). Treatment-emergent anxiety was reported for 25% of placebo patients and 7% of cotherapy patients (P<0.037); sleep disturbance for 10% of placebo patients and no cotherapy patients (P<0.055). Sedation and dry mouth were more common for cotherapy treatment (P>0.20). LIMITATIONS: Extended treatment and refractory depression were not addressed. CONCLUSIONS: Low-dose cotherapy of fluoxetine with clonazepam was safe and accelerated response over 21 days of treatment, decreasing anxiety and sleep disturbance as symptoms and partially suppressed them as SSRI side-effects; it also modestly reduced core symptoms of low mood and loss of interest.

A therapeutic milieu for chronic pain patients.

Traditional means of treating chronic pain have been unsuccessful in a discouraging number of cases. Pain centers have appeared within the last few years, offering a more comprehensive view of the whole pain problem. Pain centers address pain as a multifaceted event with social, economic, physiological, and psychological representations. In addition, the pain center constructs an atmosphere that provides every opportunity for reduction of pain, while minimizing those factors that tend to encourage its expression. Such a venture calls for a multidisciplinary approach; it further demands a rather sophisticated grasp of numerous factors which do not necessarily lend themselves to discussion with a single vocabulary. This paper will attempt to describe a number of conceptual models of chronic pain and to demonstrate how each of these models is addressed therapeutically in a multidisciplinary pain center millieu.

Multidisciplinary treatment of chronic pain at the Northwest Pain Center.

The Northwest Pain Center is a three-week multidisciplinary day care pain management program which has been operating since 1972. Experience shows that pain problems result in excessive use of medical resources, inappropriate medication use, and possibly unnecessary surgeries. Significant depression and family disruption are common. In spite of powerful incentives that maintain pain behavior, most important being the compensation and disability systems, more than 70 percent of patients maintain objective physical gains resulting from pain center treatment. Studies attempting to differentiate long-term successes from long-term failures provide implications for treatment and evaluation strategies. Areas of need are identified in public and professional education, and necessary future research.