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Biomedical subjects

K Rickels

Publications and source records attributed to K Rickels.

At least 73 records · Page 4Linked to original sources
PubMed1993

Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers.

Progesterone is readily reduced in humans to its A-ring metabolites, allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) and pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one). The latter have been reported to have anxiolytic, hypnotic and anesthetic actions when administered to laboratory animals and (or) humans. Consequently, we measured allopregnanolone and pregnanolone in 18 healthy females, ages 18-25, at the time of peak plasma progesterone following an oral dose of micronized progesterone (1,200 mg) in a double-blind, placebo-controlled study. The plasma levels of the parent steroid and metabolites were compared with changes in mood, cognition, and motor performance following progesterone administration. We observed good correlations between plasma progesterone and plasma allopregnanolone (r = 0.85), plasma pregnanolone (r = 0.81) and the combined metabolites (r = 0.92). Plasma allopregnanolone was significantly correlated with measures of fatigue, confusion and immediate recall, and these correlation coefficients were somewhat greater than those for plasma progesterone and these same behavioral measures. Significant changes in fatigue, delayed verbal recall and symbol copying were experienced by subjects who achieved high levels (> or = 95.55 nmol/l) of these anxiolytic metabolites, while those with lower metabolite levels reported no negative effects. These data suggest that allopregnanolone and pregnanolone may contribute to or mediate the observed behavioral effects of progesterone.

Administration, Oral↗
PubMed1993

Double-blind, placebo-controlled study of a once-a-day, sustained-release preparation of alprazolam for the treatment of panic disorder.

OBJECTIVE: The goals of this study were to assess the antipanic efficacy of a new, sustained-release formulation of alprazolam and to assess the safety and tolerability of once-a-day administration of 1-10 mg of sustained-release alprazolam. METHOD: One hundred ninety-four patients with diagnosis of agoraphobia with panic attacks or panic disorder with limited phobic avoidance underwent a 1-week placebo washout before being randomly assigned to groups receiving 8 weeks of double-blind treatment with either sustained-release alprazolam or placebo. RESULTS: There was a significant treatment effect favoring sustained-release alprazolam (highest mean dose = 4.7 mg/day) across almost all measures of anxiety, panic, and phobic avoidance, despite a significantly higher dropout rate in patients receiving placebo. Eighty-five percent of the patients treated with sustained-release alprazolam, compared with 61% of the patients given placebo, reported complete blockade of panic attacks by the end of 6 weeks of treatment. Sedation was the most commonly reported adverse effect. Discontinuation of sustained-release alprazolam was associated with moderate but transient levels of distress in 48% of the patients; discontinuation of placebo led to distress in only 10% of the patients. Nonetheless, there was no difference in the proportion of patients who were able to remain off the study drug for at least 2 weeks. CONCLUSIONS: These results suggest that sustained-release alprazolam is highly effective in the acute treatment of panic disorder at doses comparable to those in the originally marketed compressed tablet of alprazolam. The medication was well tolerated but showed rebound effects during a rapid drug taper after 6 weeks of treatment.

Administration, Oral↗
PubMed1993

Premenstrual symptoms and dysmenorrhea in relation to emotional distress factors in adolescents.

The extent to which premenstrual symptoms occur when they are distinguished from primary dysmenorrhea and the relationship of premenstrual symptoms to other emotional distress in adolescents is not well understood. This pilot investigation examined relationships between premenstrual symptoms, dysmenorrhea and emotional distress factors in a sample of 165 females, ages 15-19 years. Premenstrual symptoms were correlated with dysmenorrhea (r = 0.54, p < 0.0001). Subjects with premenstrual symptoms had significantly more emotional distress than the normal group as assessed by the Symptom Checklist (SCL-90), an objective self-report questionnaire. In contrast, dysmenorrhea had no relationship with the SCL factors and no interaction with premenstrual symptoms in relation to emotional distress. The SCL scores significantly decreased from baseline (2 years earlier) in the normal group but not in the premenstrual symptom group. The data show that premenstrual symptoms were associated with other emotional distress factors in adolescents while dysmenorrhea was not. A further prospective, longitudinal study of menstrually-related symptoms in adolescents is needed to learn about the development of these premenstrual symptoms that may be related to the premenstrual syndrome seen clinically in the later reproductive years.

Adolescent↗
PubMed1993

A double-blind, placebo-controlled study comparing the efficacy and safety of ipsapirone versus lorazepam in patients with generalized anxiety disorder: a prospective multicenter trial.

This multicenter, double-blind, placebo-controlled, randomized study compared the efficacy, safety, and tolerability of ipsapirone (an azapirone anxiolytic) at daily dose levels of 10.0 to 30.0 mg with a daily dose of 2.0 to 6.0 mg of lorazepam (a benzodiazepine) or placebo when given to outpatients with generalized anxiety disorder (GAD) of moderate or greater severity. A total of 317 outpatients with a primary diagnosis of GAD according to DSM-III criteria (at least 1 month's duration) were randomized. Study entry criteria at the time of screening and at baseline included a Hamilton Rating Scale for Anxiety (HAM-A) score of 18 or more, a Covi Anxiety Scale score of 8 or more, and a Raskin Depression Scale score of 7 or less. The study design consisted of a 1-week, single-blind placebo evaluation, a 4-week, double-blind acute treatment period, and a 4-week extension period, followed by a 2-week, single-blind placebo withdrawal period. Efficacy was measured by changes in the HAM-A and Clinical Global Impression Scale and by evaluations of the Hamilton Rating Scale for Depression and Zung-Anxiety Self-Rating scale. The Raskin and Covi scales were performed at screening and baseline only. Withdrawal reactions were assessed during the withdrawal period by the Physician Withdrawal Checklist and by a patient self-rating checklist. Two-hundred sixty-three patients were valid for the analysis of efficacy in the ipsapirone (N = 87), lorazepam (N = 89), and placebo (N = 87) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The treatment of generalized anxiety disorder in patients with depressive symptomatology.

Concomitant depressive symptoms occur in at least 50% of patients with a primary diagnosis of generalized anxiety disorder (GAD). The authors review the treatment implications of the presence of concomitant depressive symptoms. First considered is the extent to which traditional benzodiazepines, because of their suggested depressogenic liability, are indicated or contraindicated for such patients and the possible differential therapeutic advantage of triazolobenzodiazepines, which have shown preliminary antidepressant effect. Second, the role of tricyclic antidepressants in the treatment of GAD is reviewed. A large body of literature, mostly from the 1970s, has found benefit for the tricyclics in mixed anxiety-depression. Two studies published in the 1980s found that patients suffering from a primary anxiety diagnosis but with subsyndromic levels of depression benefited from treatment with tricyclic antidepressants. The authors also review the role of the azapirones, most notably buspirone, in the treatment of GAD complicated by depressive symptoms. Evidence for its efficacy in this population comes from both retrospective analysis of previous GAD treatment studies, as well as a recent prospective study of depression with concomitant GAD.

Antidepressive Agents, Tricyclic↗
PubMed1993

Medication discontinuation in panic disorder.

This paper addresses current issues associated with medication discontinuation in panic disorder, with specific focus on one of the most frequently used medication classes for this indication, the benzodiazepines. The majority of patients, when slowly tapered, are able to discontinue the benzodiazepines without a great deal of difficulty, particularly after short-term therapy. Patients treated with long-term therapy at high therapeutic doses may experience greater difficulty with discontinuation. If patients are adequately prepared and if discontinuation is conducted slowly and gradually, discontinuation symptoms, if they occur, are transient, mild to moderate, and generally tolerable. However, return of the original condition (relapse) during discontinuation can greatly complicate clinical management.

Alprazolam↗
PubMed1993

Gonadotropin-releasing hormone agonist in treatment of premenstrual symptoms with and without comorbidity of depression: a pilot study.

BACKGROUND: Gonadotropin-releasing hormone agonist (GnRHa) in depot form for once-a-month rather than daily injection was examined in a small open trial to determine the extent of reduction of premenstrual symptoms, particularly premenstrual "depression." METHOD: Women who met criteria for premenstrual syndrome (PMS) or for PMS with comorbidity of major depression (MD), based on DSM-III-R criteria, were evaluated for the study. Evaluation included Structured Clinical Interview for DSM-III-R, administered in the follicular phase, and Daily Symptom Report (DSR), maintained throughout the study. Seven PMS subjects and two subjects who met the severity and change criteria for PMS but had concurrent MD were administered 3.75 mg of depot leuprolide monthly. Symptom change as reported on the DSR was compared with the untreated baseline scores. RESULTS: Six of seven PMS subjects had cessation of menses and significant decreases in premenstrual symptoms (p < .0001), which were reduced to their follicular phase levels. Physical symptoms of swelling and breast tenderness were among the most improved symptoms. Despite cessation of menses, the two MD subjects showed little improvement in premenstrual symptoms and no improvement in depressive symptoms. The premenstrual depression scores decreased almost completely in the PMS subjects, but increased slightly in the MD subjects. CONCLUSION: This small open trial suggests that GnRH agonist therapy reduces premenstrual symptoms including "depression" in women who meet criteria for PMS but not in women with PMS and MD. Further controlled study of the role of ovarian function in mood disorders is needed.

Adult↗
PubMed1992

A placebo-controlled study of effects of oral progesterone on performance and mood.

1. Oral micronized progesterone (P) is proposed for the treatment of certain endocrine gynaecological disorders. To examine the effects of P on performance and mood, a randomized, placebo-controlled study of 24 healthy females ages 18-24 years on low-dose oral contraceptives was conducted. 2. Subjects were admitted to the Clinical Research Center on four occasions and received single doses of oral P (300, 600, 1200 mg) or placebo. Blood sampling, psychometric tests and mood scales were administered at baseline and at hourly intervals for 6 h. 3. P doses produced significant dose-related but highly variable increases in plasma P concentrations. Fatigue increased with P doses, although few subjects were objectively drowsy. Very high peak plasma P concentrations, achieved by some subjects at the 1200 mg dose, were associated with decreased information processing and verbal memory function as well as fatigue. 4. We conclude that oral P can safely be prescribed at higher than previously-reported doses, based on evidence of transient behavioural effects only at the highest doses in some subjects who achieved high plasma P concentrations.

Administration, Oral↗
PubMed1992

Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies.

This report presents the results of a retrospective analysis of pooled efficacy data from eight studies in which buspirone was compared to placebo in 520 patients with generalized anxiety disorder (GAD). In addition to evaluating overall efficacy in the composite patient data base, four criteria were used to identify subsets of patients with GAD who had coexisting depressive symptoms of at least moderate intensity: (1) a score of > or = 2 on the Hamilton Anxiety (HAM-A) Rating Scale item 6 (depressed mood), (2) a score of > or = 2 on the Hamilton Depression (HAM-D) Rating Scale item 1 (depressed mood), (3) a HAM-D total score of > or = 18, or (4) a HAM-D Retardation Factor value (items 1, 7, 8, and 14) greater than the median for the group. Overall, patients treated with buspirone demonstrated significant (p < or = 0.001) improvement over baseline in total HAM-A scores compared to patients who received placebo. Buspirone also produced significant (p < or = 0.001) global improvement compared to placebo as assessed by the attending physician. Of the GAD patients stratified according to the four criteria for coexisting depressive symptoms, a substantial percentage (44-64%) of the total patient sample exhibited significant depressive symptoms as part of their anxiety disorder. Patients with GAD and coexisting depressive symptoms of at least moderate intensity exhibited significantly greater improvement with buspirone compared to placebo treatment regardless of the stratification criterion used. They also responded at least as well or better to buspirone therapy as did those with GAD who had less intense depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Course of premenstrual syndrome symptom severity after treatment.

OBJECTIVE: Patients from a randomized, double-blind, placebo-controlled study of progesterone suppository treatment for premenstrual syndrome (PMS) were followed up to determine poststudy PMS symptom levels and medication use. METHOD: An average of 1 year after the end of the treatment study, 129 subjects were contacted for telephone interviews. All subjects met criteria for PMS before the progesterone suppository treatment, and their symptoms were confirmed by daily symptom reports throughout the study. The outcome measure at follow-up was the patient's global assessment of symptom severity, which was also rated by the subjects during the treatment study. The ratings at enrollment, end of study, and follow-up were compared. RESULTS: Only 27% of the subjects (N = 35) were taking medications for PMS at follow-up. Symptom severity at follow-up was less than at enrollment but greater than at the end of the study. CONCLUSIONS: Some of the improvement gained during treatment was maintained, but overall the subjects remained moderately symptomatic. Validation of the PMS condition, education, and support and caring may account for the symptom decreases during treatment, and the end of treatment and withdrawal of these conditions may account for the moderate return of symptoms.

Double-Blind Method↗
PubMed1992

Paroxetine versus placebo: a double-blind comparison in depressed patients.

BACKGROUND: Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI). The present study assessed the efficacy and tolerability of paroxetine against placebo in depressed outpatients. METHOD: A double-blind, parallel-group study was undertaken in four stand-alone centers. Patients aged 18-65 years, meeting DSM-III criteria for major depression, and having a Hamilton Rating Scale for Depression (HAM-D) score > or = 18 on the first 17 items of the HAM-D-21 were randomized to paroxetine or placebo for 6 weeks of treatment. Efficacy outcome variables included the HAM-D, the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impressions Scale (CGI), and the Covi Anxiety Scale. Tolerability was assessed by asking a non-leading question. Routine laboratory safety and vital sign data from all four centers were pooled. The primary analysis used the intention-to-treat sample and for efficacy variables the last-observation-carried-forward data set was employed. Statistical methods included one-way analysis of variance for parametric and Fisher exact test for nonparametric variables. RESULTS: Significant differences (p < or = .05) were found between paroxetine and placebo on the HAM-D and CGI by Week 2 and on all efficacy outcome variables by Week 4. Improvement on the HAM-D sleep factor occurred 2 weeks prior to that seen on the retardation factor. Similar results were obtained when an adequate treatment group (therapy for > or = 28 days) was considered. A full clinical response (CGI-severity of illness score 1 or 2) was seen in over 40% of subjects. Adverse events were more common for paroxetine compared with placebo (p < or = .01). Somnolence was twice more common than nervousness. Dropout due to adverse events was similar between therapies. Paroxetine had no clinically significant effect on laboratory safety data or vital signs. CONCLUSION: Paroxetine was an effective, well tolerated, and safe antidepressant. Side effects were typical of the SSRI class of drugs. Symptoms indicative of a nonalerting profile were more common than those associated with alerting effects.

Adolescent↗
PubMed1992

The efficacy and safety of paroxetine compared with placebo in outpatients with major depression.

Paroxetine, a phenylpiperidine derivative, is an antidepressant that selectively inhibits serotonin reuptake. In this study 111 outpatients with major depression diagnosed by DSM-III criteria were treated with either paroxetine or placebo in a 6-week, randomized, double-blind study. Paroxetine was significantly superior to placebo on six of the seven major efficacy variables. Significant differences in favor of paroxetine were apparent by Week 2. Paroxetine was also well tolerated. These results support the efficacy and safety of paroxetine as a treatment for patients with major depression.

Adult↗
PubMed1991

Carbamazepine treatment in patients discontinuing long-term benzodiazepine therapy. Effects on withdrawal severity and outcome.

Forty patients with a history of difficulty discontinuing long-term, daily benzodiazepine therapy were randomly assigned, under double-blind conditions, to treatment with carbamazepine (200 to 800 mg/d) or placebo. A gradual taper (25% per week reduction) off benzodiazepine therapy was then attempted. Five weeks after taper, significantly more patients who had received carbamazepine than placebo remained benzodiazepine free, this despite the fact that no statistically significant differences in withdrawal severity could be demonstrated. Patients receiving carbamazepine reported a larger reduction in withdrawal severity than patients receiving placebo, but only at a trend level, and only on the daily patient-rated withdrawal checklist. Eleven patients (28%) required antidepressant therapy for depression or panic when assessed at 12-weeks follow-up. The results of this pilot investigation suggest that carbamazepine might have promise as an adjunctive drug therapy for the benzodiazepine withdrawal syndrome, particularly in patients receiving benzodiazepines in daily dosages of 20 mg/d or greater of diazepam equivalents.

Benzodiazepines↗
PubMed1991

Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study.

In summary, the clinical results of this double-blind study clearly show that imipramine, as expected, demonstrated significant antidepressive properties in outpatients suffering from major depressive disorders. In contrast, adinazolam showed rather mild and weak antidepressive properties, and in no measures did its response differ significantly from that of diazepam. These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam (Rickels et al., 1987) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo, while diazepam was not. While the rather high dropout rate may well be considered a limitation of the study, the dropout rate is equally distributed between all four treatments. And since both decreasing sample size and endpoint analyses which include all patients with at least one week data, provide rather similar results, the findings can be considered as robust despite the high dropout rate. While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar, when high dropout rates occur, endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice. The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam (Covi et al., 1974) and chlordiazepoxide (Lipman et al., 1986). The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗