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Biomedical subjects

K Rickels

Publications and source records attributed to K Rickels.

At least 91 records · Page 5Linked to original sources
PubMed1991

Long-term benzodiazepine users 3 years after participation in a discontinuation program.

OBJECTIVE: Clinical status and use of benzodiazepines and other psychotropic drugs at follow-up were assessed in patients who had been chronically dependent on benzodiazepines and had been referred for participation in a discontinuation study. METHOD: Of 123 benzodiazepine-dependent patients screened for entry into a tapered discontinuation program, 48 had completed the program, 38 had not, and 37 had not undergone drug tapering. Follow-up information was obtained through a structured telephone interview and a mail questionnaire that included a global severity scale assessing anxiety and depression and the Hopkins Symptom Checklist. The time to follow-up was 2.7-5.0 years, and the mean +/- SD interval between screening and follow-up was 2.9 +/- 0.9 years. RESULTS: Outcome at follow-up significantly favored the patients who had completed the discontinuation program; 73% were not using benzodiazepines, compared to 39% in the unsuccessful taper group and 14% in the no-taper group. Moderate or marked anxiety was still reported by 35% of the patients who were taking benzodiazepines and 25% of those who were not. At follow-up, 22% of the patients were being treated with nonbenzodiazepine psychotropic agents, primarily antidepressants. CONCLUSIONS: The high percentage of patients who were benzodiazepine-free at follow-up and the continued anxiety and depression present in many patients suggest that some patients may have been taking benzodiazepines because of chronic or recurrent anxiety or depression, not physical dependence.

Anxiety Disorders↗
PubMed1991

The first double-blind, placebo-controlled trial of a partial benzodiazepine agonist abecarnil (ZK 112-119) in generalized anxiety disorder.

This is the first reported controlled trial of a partial benzodiazepine agonist, abecarnil, utilized in the treatment of generalized anxiety disorder (GAD). It was a sequential dose-finding study comparing 15-30 mg/day, 7.5-15 mg/day, and 3-9 mg/day to placebo for 3 weeks of treatment followed by abrupt discontinuation through placebo substitution. Although the two higher dose groups had high incidence of central nervous system (CNS) sedative adverse effects, the 3-9 mg/day group tolerated the medication well with no dropouts. The 3-9 mg/day group, in comparison to the two higher doses and placebo, demonstrated efficacy in global improvement ratings and Hamilton Anxiety Scale (HAM-A) scores. At Week 3, 61 percent of the abecarnil 3-9 mg/day group was rated as at least 50 percent improved on the HAM-A, compared to 30 percent of the placebo group. With abrupt discontinuation there were mild to moderate withdrawal symptoms and loss of efficacy in the two higher dose groups. However, in the 3-9 mg/day abecarnil group, there were few withdrawal symptoms and almost no loss of efficacy following discontinuation.

Adult↗
PubMed1991

Placebo-controlled trial of venlafaxine for the treatment of major depression.

Results are presented of the first double-blind, placebo-controlled trial of a novel antidepressant venlafaxine, which preclinically has demonstrated serotonin, norepinephrine, and dopamine reuptake inhibiting effects. Sixty outpatients meeting DSM-III-R criteria for major depression were randomized to receive 6 weeks of treatment with one of three fixed doses of venlafaxine--25 mg three times a day, 75 mg three times a day, or 125 mg three times a day--or placebo. Significant improvement was observed in depression scores at all doses, with the high dose resulting in earlier improvement, by week 2. For the combined venlafaxine treatment groups, 68% achieved a moderate or marked improvement on the Clinical Global Impression scale, compared with only 31% for the placebo group. Venlafaxine was well tolerated, and nervousness, sweating, and nausea were the only adverse effects observed more frequently with drug compared with placebo.

Adult↗
PubMed1991

Buspirone in major depression: a controlled study.

One hundred and fifty-five outpatients suffering from major depression with moderate anxiety entered a double-blind study comparing 8 weeks of treatment with buspirone or placebo. Thirty-four percent of buspirone and 41% of placebo patients discontinued treatment before 8 weeks. Results were consistent across all physician- and patient-completed outcome measures, with treatment response to buspirone significantly better than to placebo at treatment endpoint. Seventy percent of buspirone and 35% of placebo patients (p less than .01) were rated moderately or markedly improved after 8 weeks of therapy. Initial levels of anxiety and depression had no significant effect on treatment outcome. Buspirone was found to be safe and well tolerated at doses of up to 90 mg/day.

Adolescent↗
PubMed1990

Ineffectiveness of progesterone suppository treatment for premenstrual syndrome.

Progesterone is the most widely used treatment for premenstrual syndrome. To answer definitely the question of whether progesterone suppositories are effective for the treatment of premenstrual syndrome, a randomized, placebo-controlled, double-blind crossover study of 168 women, receiving progesterone in doses of 400 and 800 mg or placebo, was carried out. Premenstrual symptoms were not significantly improved by progesterone compared with placebo in any measure used in the study, including daily symptom reports maintained throughout treatment, clinician evaluation of improvement, and patient global reports of symptoms severity, relief, and disruption of daily activity. No symptom cluster or individual symptom differed significantly between progesterone and placebo treatment. These treatment results were not significantly affected by fluctuations in response during the placebo washout period, pretreatment levels of depression or anxiety at either postmenstrual or premenstrual times, or any of 19 other background, medical history, or symptom variables examined individually as covariates with treatment.

Adult↗
PubMed1990

Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation.

We compared the effect of abrupt discontinuation of therapeutic doses of short half-life and long half-life benzodiazepines in 57 benzodiazepine-dependent patients (daily use, greater than 1 year). Despite the use of a mean daily dose of 14.1 mg of diazepam equivalents, there were notable residual symptoms of anxiety and depression present at intake (Hamilton Rating Scale for Anxiety score, 17.0; Hamilton Rating Scale for Depression score, 14.0). Benzodiazepine intake was stabilized for 3 weeks before double-blind assignment to placebo (n = 47), or continued benzodiazepine use (n = 10). Clinical assessments were performed daily, including benzodiazepine plasma levels. Depending on the outcome criteria used, anywhere from 58% to 100% of patients were judged to have experienced a withdrawal reaction, with a peak severity at 2 days for short half-life and 4 to 7 days for long half-life benzodiazepines. Relapse onto benzodiazepines occurred in 27% of patients who were receiving long half-life benzodiazepines and in 57% of patients who were receiving short half-life benzodiazepines. Baseline predictors of relapse were nonpanic diagnoses, a higher benzodiazepine dose, and a higher Eysenck neuroticism score. A short half-life and higher daily doses were associated with greater withdrawal severity, as were personality traits, such as dependency and neuroticism, less education and higher baseline levels of anxious and depressive symptoms. Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower levels of anxiety than before benzodiazepine discontinuation. These results provide a detailed picture of the symptoms, time course, and multidimensional determinants of the benzodiazepine withdrawal syndrome.

Ambulatory Care↗
PubMed1990

Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper.

We compared the effect on withdrawal severity and acute outcome of a 25% per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine-dependent patients. Patients unable to tolerate taper were permitted to slow the taper rate. Ninety percent of patients experienced a withdrawal reaction, but it was rarely more than mild to moderate. Nonetheless, 32% of long half-life and 42% of short half-life benzodiazepine-treated patients were unable to achieve a drug-free state. The most difficulty was experienced in the last half of taper. Baseline personality, high Eysenck neuroticism, female sex, and mild-to-moderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life. These findings suggest that personality factors contribute significantly to the patient's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines.

Adult↗
PubMed1990

Lorazepam vs. alprazolam in the treatment of panic disorder.

Sixty-seven patients with panic disorder were treated with single-blind placebo for one week before being randomized to 6 weeks of double-blind treatment with either lorazepam or alprazolam. Both drugs showed significant and comparable antipanic efficacy throughout the course of the study. With the exception of sedative effects, both drugs were well-tolerated at a mean daily dose of 7 mg for lorazepam and 3 mg for alprazolam. Lorazepam appeared to be as effective as alprazolam in the acute treatment of panic disorder.

Adult↗
PubMed1990

Clinical effects of the 5-HT1A partial agonists in depression: a composite analysis of buspirone in the treatment of depression.

The azapirone class of anxiolytic drugs is being evaluated for clinical use in the treatment of depression. Buspirone, a serotonin (5-hydroxytryptamine, 5-HT) partial agonist active at the 5-HT1A receptor subtype, was evaluated in the treatment of depression in a series of five placebo-controlled, parallel group studies involving 382 patients with DSM-III major depression and significant associated anxiety symptoms (both Hamilton depression [HAM-D] and Hamilton anxiety [HAM-A] scales greater than or equal to 18). Buspirone therapy was initiated at 15 mg/day with individual dose titration to a maximum of 90 mg/day and resulted in marked improvement in both depressive and anxiety symptoms. Analyses of the composite data base from the five studies show significant (p less than 0.05) improvement in mean HAM-D, HAM-A, and Clinical Global Impression-Global Improvement scale ratings for buspirone-treated compared with placebo-treated patients. Of particular interest was significant improvement in cardinal depression symptoms, e.g., depressed mood, guilt, work and interest, anergia, and diurnal variation of mood. Subset analyses revealed that patients with melancholic-type major depression and patients with more severe symptoms (judged by higher initial HAM-D or HAM-A total scores) responded better to buspirone than did patients who were less ill. The buspirone dose most frequently associated with clinically significant improvement was 40 mg/day. Gepirone, an analogue of buspirone with highly selective binding affinity for the 5-HT1A receptor subtype, also shows promise of antidepressant efficacy in preliminary controlled clinical trials. These data suggest that azapirones, which as partial agonists modulate 5-HT1A receptor function, have clinically important antidepressant properties.

Adolescent↗
PubMed1990

Benzodiazepine dependence: management of discontinuation.

This article discusses the management of benzodiazepine (BZ) withdrawal in patients who are chronically benzodiazepine dependent. Gradual benzodiazepine discontinuation is preferable to abrupt discontinuation, particularly for patients on short half-life benzodiazepines. For a small number of patients, replacement of short half-life with long half-life benzodiazepines may also be helpful. Finally, we present new preliminary data from a controlled, double-blind study that suggest that adjunctive use of such drugs as carbamazepine, imipramine, and buspirone may be helpful in managing gradual benzodiazepine discontinuation. Initiating adjunctive medication prior to, and continuing it during and after benzodiazepine discontinuation led to significantly higher discontinuation success rates for carbamazepine (91%), buspirone (85%), and imipramine (79%) than for placebo (58%) (p less than .05). Careful followup for an extended period of time is needed after benzodiazepine discontinuation because, frequently, emerging psychiatric symptoms may again necessitate psychiatric intervention.

Anti-Anxiety Agents↗
PubMed1990

The clinical course and long-term management of generalized anxiety disorder.

Evidence suggests that generalized anxiety disorder (GAD) has a fairly chronic course marked by significant long-term distress and comorbidity. Research has focused on short-term treatment of GAD, and long-term outcome studies after either short- or long-term treatment have been relatively neglected. The authors discuss the benefits and risks of various drug and nondrug therapies used in the long-term management of generalized anxiety disorder and suggest avenues for future research.

Anti-Anxiety Agents↗
PubMed1990

Clinical overview of serotonin reuptake inhibitors.

The clinical pharmacology, adverse event profiles, and clinical efficacy of several serotonin reuptake inhibitors are summarized and compared with those of the classic tricyclic antidepressants. Serotonin reuptake inhibitors discussed are sertraline, zimelidine, fluoxetine, fluvoxamine, and paroxetine. While they do not differ from tricyclics in efficacy or onset of action, the serotonin reuptake inhibitors clearly have a different side effect potential. Unlike tricyclics, serotonin reuptake inhibitors provide effective antidepressant activity without sedating, anticholinergic, or cardiotoxic reactions. In comparison, tricyclics lower the seizure threshold, have anticholinergic and hypotensive effects, affect cardiac conduction, are dangerous in overdose, and may cause weight gain. The primary adverse events associated with serotonin reuptake inhibitors involve the gastrointestinal system, although side effects may be less frequent at lower dosage levels. It is important to choose antidepressant therapy on the basis of a patient's ability to tolerate the specific adverse reactions that may occur with a given agent. Although serotonin reuptake inhibitors have not replaced the tricyclics, they are a useful addition to the variety of drugs currently used for the treatment of depression.

1-Naphthylamine↗
PubMed1990

Buspirone in clinical practice.

Buspirone, an azapirone derivative and a 5-HT1A partial agonist, is the first nonbenzodiazepine anxiolytic introduced into medicine for the treatment of generalized anxiety disorder. A series of well-controlled clinical trials demonstrated that its anxiolytic properties were similar to those of various benzodiazepines and significantly better than placebo. More recently, antidepressant effects were also observed. Patients with clinical indications for which buspirone seems to be particularly appropriate are those with generalized anxiety disorder, those with chronic anxiety, the anxious elderly, and, perhaps, many patients of all ages who suffer from mixed symptoms of anxiety and depression. Studies conducted with patients suffering from panic disorder have so far been inconclusive, and thus buspirone is, for the present at least, not recommended for routine treatment of panic disorder. Buspirone seems to be most helpful in anxious patients who do not demand immediate gratification or the immediate relief they associate with the benzodiazepine response. Slower and more gradual onset of anxiety relief is balanced by the increased safety and lack of dependency-producing aspects of buspirone. Finally, whether or not buspirone may possess "curative" properties, in addition to "anxiety-suppressant" properties, that allow the patient to improve coping skills with time requires further exploration.

Anxiety Disorders↗
PubMed1990

Buspirone in depressed outpatients: a controlled study.

One hundred fifty-five outpatients suffering from major depression with significant anxiety entered a double-blind study comparing 8 weeks of treatment with buspirone or placebo. Twenty-nine percent of buspirone and 40 percent of placebo patients discontinued treatment before 8 weeks. Major efficacy measures were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D retardation and anxiety factors, the HAM-D Rickels and Bech core depression clusters, the Clinical Global Impressions (CGI), and the Hopkins Symptom Checklist (HSCL). Results were consistent across all outcome measures, including the two core depression clusters, with treatment response to buspirone significantly better than to placebo at treatment endpoint. Seventy percent of buspirone and 35 percent of placebo patients (p less than .01) were rated moderately or markedly improved after 8 weeks of therapy. Buspirone was found to be safe and well-tolerated by patients with major depression and concomitant anxiety at doses of up to 90 mg/day.

Anxiety Disorders↗
PubMed1990

A placebo-controlled study of enciprazine in the treatment of generalized anxiety disorder: a preliminary report.

Enciprazine is a propanolamine derivative with a preclinical profile similar to buspirone but with less affinity for the postsynaptic dopamine receptor (Linden et al. 1988). We report on the outcome, using intent-to-treat data, of a 5-week, double-blind trial comparing three dose strengths of enciprazine (5 mg t.i.d., 10 mg t.i.d., and 20 mg t.i.d.) to placebo. A dose escalation was permitted after 2 weeks of active drug treatment, which 61 percent of patients overall took advantage of. A "last observation carried forward" (LOCF) analysis found a mean improvement in Hamilton Anxiety Scale (HAM-A) scores by Week 5 of -11.0 for the combined enciprazine treatment groups, and -4.4 for the placebo group (p less than .05). Fifty-two percent of enciprazine patients were judged to be "much" or "very much" improved, whereas none of the placebo patients were judged to have comparable improvement. Enciprazine was well-tolerated, with low levels of sedative and asthenic side effects reported. The compound appears to have promise as an anxiolytic agent.

Adult↗
PubMed1990

What constitutes an adequate antidepressant trial for fluoxetine?

One hundred and eight patients with major depression were treated with fluoxetine 20 mg/day for 3 weeks. Patients who failed to respond to this open-label treatment were randomly assigned either to receive fluoxetine 60 mg/day for 5 weeks or to continue treatment with fluoxetine 20 mg/day for an additional 5 weeks. Both treatment groups demonstrated a statistically significant reduction in depressive symptoms, indicating that continued treatment with low-dose fluoxetine may be as effective as an increase in dose in achieving a favorable clinical outcome.

Adult↗