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K Rickels

Publications and source records attributed to K Rickels.

At least 19 recordsLinked to original sources

Abnormal salivary cortisol levels in social phobic patients in response to acute psychological but not physical stress.

BACKGROUND: Little is known about the hypothalamic-pituitary-adrenal axis response to acute stressful behavioral challenges in patients with social phobia. METHODS: Eighteen patients with social phobia and 17 normal volunteers participated in two behavioral stressors: a speech task and physical exercise. RESULTS: Normal volunteers (n = 14) demonstrated a significant 50% increase in salivary cortisol levels to the speech task. Three nonresponding normal volunteers demonstrated a 17% decrease. In contrast, patients with social phobia demonstrated dichotomous changes. Seven social phobia patients demonstrated a significantly higher 90% increase in salivary cortisol to the speech task, whereas the remaining patients (n = 11) were nonresponders demonstrating a 32% decrease in cortisol. Both patient groups were significantly more anxious than the normal volunteers. In contrast to the response to a speech task, social phobics showed a cortisol response to physical exercise of similar magnitude as normal volunteers. CONCLUSIONS: The results indicated dichotomies in magnitude and in distribution of the cortisol response to a speech task between social phobia patients and normal volunteers. Social phobia patients responded differently than normal volunteers to a stressor associated with social evaluation but not to physical exercise. These results suggest adaptation of distinct biological processes specific to different stressful conditions in social phobia.

Acute Disease↗

Venlafaxine in the treatment of premenstrual dysphoric disorder.

OBJECTIVE: To evaluate the efficacy and safety of venlafaxine, a new-generation antidepressant that selectively inhibits serotonin and norepinephrine reuptake, in the treatment of premenstrual dysphoric disorder (PMDD). METHOD: We conducted a randomized, double-blind, placebo-controlled, parallel-group, flexible-dose trial. After three screening cycles, including a single-blind placebo cycle, 164 women were randomly assigned to double-blind treatment with venlafaxine (50-200 mg/day) or placebo for four menstrual cycles. Primary outcome measures were the total premenstrual symptom scores as assessed by a daily symptom report (DSR) and the Hamilton Rating Scale for Depression. RESULTS: Venlafaxine was significantly more effective than placebo in reducing PMDD symptoms as assessed by DSR scores (P <.001 for last observation carried forward and observed analyses). Sixty percent of venlafaxine versus 35% of placebo subjects improved >50% (P =.003). Forty-three percent of venlafaxine subjects versus 25% of placebo subjects experienced symptom remission, defined as reduction of DSR scores to the postmenstrual level (P =.034). Venlafaxine treatment was significantly better than placebo for all statistically derived DSR factors (mood, function, pain, and physical symptoms). Improvement was relatively swift, with approximately 80% symptom reduction in the first treatment cycle. Mean venlafaxine doses ranged from 50 mg/day in the first treatment cycle to 130 mg/day in the fourth treatment cycle. Adverse events such as nausea, insomnia, and dizziness were mild and transient. CONCLUSIONS: Venlafaxine is significantly more efficacious than placebo for PMDD treatment. Response to treatment can occur in the first treatment cycle, and venlafaxine is well tolerated. Further studies are needed to evaluate the potential of intermittent (luteal phase) dosing for this cyclic disorder and the efficacy of long-term maintenance treatment with venlafaxine.

Adult↗

Overview and clinical presentation of generalized anxiety disorder.

1. To distinguish GAD from panic disorder is not difficult if a patient has frequent, spontaneous panic attacks and agoraphobic symptoms, but many patients with GAD have occasional anxiety attacks or panic attacks. Such patients should be considered as having GAD. An even closer overlap probably exists between GAD and social phobia. Patients with clear-cut phobic avoidant behavior may be distinguished easily from patients with GAD, but patients with social anxiety without clear-cut phobic avoidant behavior may overlap with patients with GAD and possibly should be diagnosed as having GAD and not social phobia. The cardinal symptoms of GAD commonly overlap with those of social phobia, particularly if the social phobia is more general and not focused on a phobic situation. For example, free-floating anxiety may cause the hands to perspire and may cause a person to be shy in dealing with people in public, and thus many patients with subthreshold social phobic symptoms have, in the authors' opinion, GAD and not generalized social phobia. The distinction between GAD and obsessive-compulsive disorder, acute stress disorder, and posttraumatic stress disorder should not be difficult by definition. At times, however, it may be difficult to distinguish between adjustment disorder with anxious mood from GAD or anxiety not otherwise specified, particularly if the adjustment disorder occurs in a patient with a high level of neuroticism or trait anxiety or type C personality disorder. Table 2 presents features distinguishing GAD from other psychiatric disorders. 2. Lifetime comorbid diagnoses of other anxiety or depression disorders, not active for 1 year or more and not necessitating treatment during that time period, should not effect a diagnosis of current GAD. On the other hand, if concomitant depressive symptoms are present and if these are subthreshold, a diagnosis of GAD should be made, and if these are full threshold, a diagnosis of MDD should be made. 3. If GAD is primary and if no such current comorbid diagnosis, such as other anxiety disorders or MDD, is present, except for minor depression and dysthymia, or if only subthreshold symptoms of other anxiety disorders are present, GAD should be considered primary and treated as GAD; however, patients with concurrent threshold anxiety or mood disorders should be diagnosed according to the definitions of these disorders in the DSM-IV and ICD-10 and treated as such. 4. Somatization disorders are now classified separately from anxiety disorders. Some of these, particularly undifferentiated somatization disorder, may overlap with GAD and be diagnostically difficult to distinguish. The authors believe that, as long as psychic symptoms of anxiety are present and predominant, patients should be given a primary diagnosis of GAD. 5. Two major shifts in the DSM diagnostic criteria for GAD have markedly redefined the definition of this disorder. One shift involves the duration criterion from 1 to 6 months, and the other, the increased emphasis on worry and secondary psychic [table: see text] symptoms accompanied by the elimination of most somatic symptoms. This decision has had the consequence of orphaning a large population of patients suffering from GAD that is more transient and somatic in its focus and who typically present not to psychiatrists but to primary care physicians. Therefore, clinicians should consider using the ICD-10 qualification of illness duration of "several months" to replace the more rigid DSM-IV criterion of 6 months and to move away from the DSM-IV focus on excessive worry as the cardinal symptom of anxiety and demote it to only another important anxiety symptom, similar to free-floating anxiety. One also might consider supplementing this ICD-10 criterion with an increased symptom severity criterion as, for example, a Hamilton Anxiety Scale of 18. Finally, the adjective excessive, not used in the definition of other primary diagnostic criteria, such as depressed mood for MDD, should be omitted (Table 3). 6. One may want to consider the distinction of trait (chronic) from state (acute) anxiety, but whether the presence of some personality characteristics, particularly anxious personality or Cluster C personality and increased neuroticism, as an indicator of trait [table: see text] anxiety is a prerequisite for anxiety disorders; occurs independently of anxiety disorders; or is a vulnerability factor that, in some patients, leads to anxiety symptoms and, in others, does not, is unknown. 7. Symptoms that some clinicians consider cardinal for a diagnosis of GAD, such as extreme worry, obsessive rumination, and somatization, also are present in other disorders, such as MDD. (ABSTRACT TRUNCATED)

Anxiety↗

The antidepressant effect of sertraline is not enhanced by dose titration: results from an outpatient clinical trial.

A previous report suggested that 5 weeks of continued treatment with 20 mg of fluoxetine was approximately as effective as double-blind titration to a dose of 60 mg in patients who had failed to respond to 3 weeks of initial treatment at 20 mg. The current study was undertaken to evaluate whether 150 mg of sertraline was any more effective than 50 mg in treating depressed patients who were non-responders at 3 weeks. Ninety-one outpatients with DSM-IV major depressive disorder who had a 17-item Hamilton Depression Rating Scale (HAM-D) score > or = 18 were treated with open label sertraline for 3 weeks. Patients who did not achieve remission (defined as 17-item HAM-D total score < or = 8 by week 3) were then randomized to 5 more weeks of double-blind treatment with either 50 mg of sertraline or immediate titration to 150 mg of sertraline. Efficacy was assessed at each visit with the HAM-D, Clinical Global Impressions (CGI)-severity and improvement scale, and the Hopkins Symptom Checklist. There were no significant between-group differences in clinical or demographic features at baseline for the three treatment groups. After 3 weeks of open-label treatment, 16 patients were not randomized, of whom 11 (69%) met responder criteria. The remaining patients were randomized, double-blind, to 50 mg of sertraline (n = 37; HAM-D = 19.2 +/- 5.0) or 150 mg of sertraline (n = 38; HAM-D = 18.4 +/- 5.0). PROC-Mixed analyses found no significant difference in slopes for any outcome measure when comparing 50 mg and 150 mg sertraline treatment groups. At week 8 (LOCF), the overall remission rate (HAM-D < or = 8) for 3-week non-responders was 40%, with no statistically significant between-group difference for the 50 mg versus 150 mg doses of sertraline (P > 0.10). A completer analysis yielded similar results. Adverse events were mostly mild on both doses of sertraline and led to few treatment discontinuations. The results suggest that for most patients continued treatment with 50 mg dose of sertraline yields a rate of antidepressant response that is comparable to what is achieved by dose escalation from 50 mg to 150 mg of sertraline after 3 weeks of treatment. While some patients clearly benefit from higher doses, the results of the current study are consistent with the lack of any evidence for a dose-response curve with sertraline in the treatment of depression.

Adult↗

Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder.

OBJECTIVE: The study compared the safety and efficacy of sertraline, a selective serotonin reuptake inhibitor, and placebo in the treatment of generalized anxiety disorder in children and adolescents. METHOD: The study subjects were 22 children and adolescents age 5-17 years who met the DSM-IV criteria for generalized anxiety disorder according to the Anxiety Disorders Interview Schedule for Children-Revised and who had a Hamilton Anxiety Rating Scale score > or = 16. The patients underwent a 2-3-week prestudy evaluation period, followed by a 9-week double-blind treatment phase in which they were randomly assigned in blocks of four to receive either sertraline or pill placebo. The maximum dose of sertraline was 50 mg/day. Primary outcome measures were the Hamilton anxiety scale and the Clinical Global Impression scale. RESULTS: The Hamilton anxiety scale total score, psychic factor, and somatic factor and the Clinical Global Impression severity and improvement scales showed significant differences with treatment in favor of sertraline over placebo beginning at week 4. Self-report measures reflected these results at the end of treatment. CONCLUSIONS: The results of this double-blind, placebo-controlled trial suggest that sertraline at the daily dose of 50 mg is safe and efficacious for the treatment of generalized anxiety disorder in children and adolescents.

Adolescent↗

What is generalized anxiety disorder?

Generalized, persistent, and free-floating anxiety was first described by Freud in 1894, although the diagnostic term generalized anxiety disorder (GAD) was not included in classification systems until 1980 (Diagnostic and Statistical Manual for Mental Disorders, Third Edition [DSM-III]). Initially considered a residual category to be used when no other diagnosis could be made, it is now widely accepted that GAD represents a distinct diagnostic category. Since 1980, revisions to the diagnostic criteria for GAD in the DSM-III-R and DSM-IV classifications have markedly redefined this disorder, increasing the duration criterion to 6 months and increasing the emphasis on worry and psychic symptoms. This article reviews the development of the diagnostic criteria for defining GAD from Freud to DSM-IV and compares the DSM-IV criteria with the criteria set forth in the tenth revision of the International Classification of Diseases. The impact of the changes in diagnostic criteria on research into GAD, and on diagnosis, differential diagnosis, and treatment of GAD, will be discussed.

Anxiety Disorders↗

Consensus statement on generalized anxiety disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in generalized anxiety disorder (GAD) and guide clinical practice with recommendations on the appropriate treatment strategy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R.T. Davidson, Yves Lecrubier, and David J. Nutt. Four additional faculty members invited by the chair were Karl Rickels, Hans-Ulrich Wittchen, Dan J. Stein, and Thomas D. Borkovec. EVIDENCE: The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSIONS: GAD is the most common anxiety disorder in primary care and is highly debilitating. Furthermore, it is frequently comorbid with depression and other anxiety disorders, which exacerbates functional impairment. Antidepressants (serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and nonsedating tricyclic antidepressants) are generally the most appropriate first-line pharmacotherapy for GAD, since they are also effective against comorbid psychiatric disorders and are suitable for long-term use. Cognitive-behavioral therapy is the preferred form of psychotherapy for GAD, although when GAD is comorbid with depression, pharmacotherapy is increasingly indicated.

Age of Onset↗

Elevated plasma thymopoietin associated with therapeutic nonresponsiveness in major depression.

BACKGROUND: Stress predisposes to major depression, and hyperactivity of the stress-activated hypothalamic-pituitary-adrenal (HPA) axis occurs in this disease. Thymopentin, an active fragment of thymopoietin (TP), reduces endocrine and behavioral responses to experimental stress, possibly by lowering plasma TP (pTP) levels. METHODS: Plasma TP and the HPA hormones arginine vasopressin (pAVP), adrenocorticotropic hormone (pACTH), and plasma cortisol (pCORT) were measured in 21 untreated depressed patients and 21 matched control subjects. Clinical responses to antidepressants were evaluated in 17 depressed patients. RESULTS: Plasma TP was elevated in depression (p < .002), with in 8 out of 21 (38%) depressed patients having significant elevations (p < .03). For 17 patients whose antidepressant responses were evaluated, nonresponsiveness occurred in 6 out of 7 (86%) with elevated pTP (>7.5 pg/mL) versus 3 out of 10 (30%) with normal pTP (p < .05). CONCLUSIONS: The significant association of elevated pTP with nonresponsiveness to antidepressant drugs may signify a distinct pathogenesis for the depression of patients with elevated pTP.

Adrenocorticotropic Hormone↗

A double-blind, placebo-controlled trial of abecarnil and diazepam in the treatment of patients with generalized anxiety disorder.

In a multicenter, double-blind trial, 310 patients who had received a diagnosis of generalized anxiety disorder were treated for 6 weeks with either abecarnil, diazepam, or placebo at mean daily doses of 12 mg of abecarnil or 22 mg of diazepam administered three times daily. Patients who were improved at 6 weeks could volunteer to continue double-blind treatment for a total of 24 weeks. The maintenance treatment phase allowed the comparison of taper results for the three treatments at several study periods (0-6 weeks, 7-12 weeks, and more than 12 weeks). Slightly more diazepam (77%) and placebo (75%) patients completed the 6-week study than abecarnil patients (66%). At intake and baseline, after a 1-week placebo washout, the patient was required to have a Hamilton Rating Scale for Anxiety score of > or =20. Major adverse events for both abecarnil and diazepam were drowsiness, dizziness, fatigue, and coordination difficulties. Clinical improvement data showed that both abecarnil and diazepam produced statistically significantly more symptom relief than did placebo after 1 week of treatment. At 6 weeks treatment (using last observation carried forward analysis), however, only diazepam still differed significantly (p < 0.01) from placebo. High placebo response (56% moderate to marked global improvement) at 6 weeks, as well as a slightly lower nonsignificant improvement rate observed with abecarnil, a partial y-aminobutyric acid (GABA) agonist, when compared with diazepam, a full GABA agonist, most likely contributed to our findings. Finally, taper results showed that only diazepam and not abecarnil caused the presence of temporary discontinuation symptoms, but only in patients who had been treated for at least 12 weeks.

Adolescent↗

Imipramine and buspirone in treatment of patients with generalized anxiety disorder who are discontinuing long-term benzodiazepine therapy.

OBJECTIVE: Patients with generalized anxiety disorder (N=107) who had been long-term benzodiazepine users (average duration of use=8.5 years) were enrolled in a benzodiazepine discontinuation program that assessed the effectiveness of concomitant imipramine (180 mg/day) and buspirone (38 mg/day) compared to placebo in facilitating benzodiazepine discontinuation. METHOD: After a benzodiazepine stabilization period taking either diazepam, lorazepam, or alprazolam, patients were treated for 4 weeks with imipramine, buspirone, or placebo under double-blind conditions while benzodiazepine intake was kept stable (treatment phase). Patients then entered a 4-6 week benzodiazepine taper and a 5-week posttaper phase with imipramine, buspirone, and placebo treatment being continued until 3 weeks into the posttaper phase, at which time all patients were switched to placebo for 2 weeks. Benzodiazepine plasma levels were assayed weekly. Benzodiazepine-free status was assessed 3 and 12 months posttaper. RESULTS: Study subjects were long-term benzodiazepine users with an average of three unsuccessful prior taper attempts. The success rate of the taper in this study was significantly higher for patients who received imipramine (82.6%), and nonsignificantly higher for patients who received buspirone (67.9%), than for patients who received placebo (37.5%). The imipramine effect remained highly significant even after the analysis adjusted for three other independent predictors of taper success: benzodiazepine dose, level of anxious symptoms at baseline, and duration of benzodiazepine therapy. CONCLUSIONS: Management of benzodiazepine discontinuation can be facilitated significantly by co-prescribing imipramine before and during the benzodiazepine taper. Daily benzodiazepine dose, severity of baseline symptoms of anxiety and depression, and duration of benzodiazepine use were additional significant predictors of successful taper outcome.

Adult↗

Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder.

OBJECTIVE: This study evaluated the efficacy and safety of fixed doses of once-daily extended-release (XR) venlafaxine in outpatients with generalized anxiety disorder without concomitant major depressive disorder. METHOD: Adult outpatients with generalized anxiety disorder but not major depressive disorder with total scores of 18 or higher on the Hamilton Rating Scale for Anxiety and scores of 2 or higher on its anxious mood and tension factors were eligible. Patients were randomly assigned to receive placebo or venlafaxine XR (75, 150, or 225 mg/day) for 8 weeks. Primary efficacy variables were final total and psychic anxiety factor scores on the Hamilton anxiety scale and final severity and global improvement item scores on the Clinical Global Impression (CGI) scale. RESULTS: Of the 377 patients entering the study, 370 were included in a safety analysis and 349 in an efficacy analysis. Adjusted mean scores at 8 weeks (last-observation-carried-forward analysis) were significantly lower for one or more of the venlafaxine XR groups in four of four primary and three of four secondary outcome measures than for the placebo group. These included a change of 1.7 (versus 1.3) from baseline on CGI severity item scores and a final score of 2.2 (versus 2.6) on the CGI global improvement item. All doses of venlafaxine XR were well tolerated. CONCLUSIONS: Venlafaxine XR is an effective and well-tolerated option for the short-term treatment of generalized anxiety disorder in outpatients without major depressive disorder.

Adult↗

Prior benzodiazepine use and buspirone response in the treatment of generalized anxiety disorder.

BACKGROUND: An earlier preliminary report suggested that prior treatment with benzodiazepines might predict a reduced response to buspirone in patients diagnosed with generalized anxiety disorder (GAD). To confirm or refute this hypothesis, the present data analysis was conducted. METHOD: One large data set (N = 735) of GAD patients (DSM-III) treated with buspirone, a benzodiazepine, and a placebo was analyzed by dividing all patients into 3 prior benzodiazepine (BZ) treatment groups: no prior BZ treatment, recent (< 1 month) BZ treatment, and remote (> or = 1 month) BZ treatment. Using an intent-to-treat last-observation-carried-forward (LOCF) data set, acute 4-week treatment response was assessed in terms of clinical improvement, attrition, and adverse events as a function of these 3 prior benzodiazepine treatment groups. RESULTS: Patient attrition was significantly higher (p < .05) in the recent BZ treatment group than in the remote and no prior BZ treatment groups with lack of efficacy given as the primary reason by patients receiving buspirone but not benzodiazepine or placebo. In the buspirone group, adverse events occurred more frequently in the recent BZ treatment group than in the remote BZ treatment and no prior BZ treatment groups. Finally, clinical improvement with buspirone was similar to benzodiazepine improvement in the no prior BZ treatment and remote BZ treatment groups, but less than benzodiazepine improvement in the recent BZ treatment group, leading to the smallest buspirone/placebo differences in improvement in the recent BZ treatment group. CONCLUSION: These data suggest that the initiation of buspirone therapy in GAD patients who have only recently terminated benzodiazepine treatment should be undertaken cautiously and combined with appropriate patient education.

Adolescent↗

Prior benzodiazepine exposure and benzodiazepine treatment outcome.

BACKGROUND: We examined discontinuation symptoms following brief benzodiazepine therapy (8 weeks) and intermittent benzodiazepine therapy (2 weeks with at least 2 weeks without drug) and associations with prior benzodiazepine use. The hypothesis was that prior benzodiazepine use would predispose patients to more severe discontinuation symptoms. METHOD: Data were drawn from 3 double-blind, randomized, placebo-controlled, published treatment trials: alprazolam for patients with premenstrual syndrome (PMS) and diazepam and lorazepam for patients with generalized anxiety disorder (GAD). The PMS group provided prospective daily symptom ratings, which allowed ongoing investigation of effects of prior treatment. In the GAD groups, taper outcome was examined after 8 weeks of benzodiazepine therapy as a function of prior benzodiazepine use and as a function of time since last prior benzodiazepine use. Symptom scores were analyzed using t statistics in the PMS group and analysis of covariance with 8-week scores as the covariate in the GAD groups. RESULTS: The PMS subjects reported no increase in symptom scores and no significant difference from placebo-treated subjects during taper and discontinuation of alprazolam in the follicular phase of each treatment cycle. In the GAD trials, the results of treatment discontinuation did not differ significantly as a function of presence or absence of prior benzodiazepine use or as a function of time since last benzodiazepine use. CONCLUSION: These preliminary data fail to support the hypothesis that prior benzodiazepine use predisposes patients to more severe discontinuation symptoms when treatment is brief and doses are low.

Alprazolam↗

Differential response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder: a randomized controlled trial.

BACKGROUND: Studies show that selective serotonin reuptake inhibitors are effective for severe premenstrual syndrome and premenstrual dysphoric disorder. This study compares the efficacy of a selective serotonin reuptake inhibitor with that of a tricyclic antidepressant to determine whether efficacy for premenstrual syndrome/premenstrual dysphoric disorder is a general or more serotonergic effect of antidepressants. METHODS: After 3 screening months, 189 subjects were randomized to sertraline hydrochloride, desipramine hydrochloride, or placebo for 3 months of double-blind treatment. The flexible dosage range was 50 to 150 mg/d. The outcome measures included the Penn Daily Symptom Report (DSR), the Hamilton Depression Rating Scale, the Clinical Global Impressions-Severity Scale, the Quality of Life Scale, and Patient Global Ratings of Functioning and Improvement. Analyses included all subjects with treatment data, with the last observation carried forward. RESULTS: Sertraline was significantly more effective than placebo or desipramine; desipramine was not better than placebo (F2,163 = 12.47, P<.001). All DSR factors were more improved with sertraline compared with desipramine and placebo; the factors for mood (P<.001) and pain (P = .05) were significant, and the results of all outcome measures were consistent. A history of depression, postmenstrual symptom levels, and other diagnostic variables added individually as covariates did not alter the treatment results. At end point analysis, DSR symptoms had decreased by more than 50% in 40 subjects (65%) in the sertraline group, 18 subjects (36%) in the desipramine group, and 16 subjects (29%) in the placebo group (P<.001). CONCLUSIONS: The comparison of 2 classes of antidepressants strongly favored the serotonergic drug, which effectively reduced symptoms and improved functioning and was well tolerated by women with severe premenstrual syndrome. A history of depression did not alter the treatment results.

Antidepressive Agents, Second-Generation↗

Trazodone and valproate in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal symptoms and taper outcome.

Recent uncontrolled research suggested that trazodone and sodium valproate may be helpful in benzodiazepine (BZ) discontinuation. We therefore undertook a double-blind study to assess whether trazodone and valproate, as compared to placebo, would attenuate withdrawal and facilitate discontinuation in BZ-dependent patients with a minimum of 1 year daily BZ use. Seventy-eight patients, taking a mean dose of 19+/-17 mg/day of diazepam (or its equivalent), were stabilized for several weeks on their BZ (16 diazepam, 25 lorazepam, 37 alprazolam) and then for 1-2 weeks, pretreated with trazodone, sodium valproate or placebo before being tapered at 25% per week. All treatments were continued for 5 weeks post-taper. BZ-free status was assessed after 5 and 12 weeks post-taper. Neither trazodone nor valproate had any significant effect on withdrawal severity. Peak physician withdrawal checklist change from baseline to peak severity was 16.4 for trazodone, 18.04 sodium valproate and 18.24 placebo (F = 0.10; NS). Taper success rates were significantly effected by both active agents at the 5-week, but not 12-week, assessment. At 5 weeks post-taper, 79% of sodium valproate and 67% of trazodone, but only 31% of placebo patients were BZ-free (chi2 = 7.34; df 2; P<0.03). Major adverse events for trazodone were sedation and dry mouth, and for valproate, diarrhea, nausea and headaches.

Adult↗

Full- or half-cycle treatment of severe premenstrual syndrome with a serotonergic antidepressant.

Evidence that serotonergic antidepressants are effective for treating premenstrual syndrome (PMS) raises the question of whether dosing only in the symptomatic premenstrual phase is effective for this disorder. This preliminary randomized, double-blind study compared the responses to half-cycle or full-cycle dosing of sertraline in 31 patients who completed a preceding double-blind, short-term treatment trial. The subjects fulfilled criteria for severe PMS when they entered the preceding controlled trial. At the end of the short-term treatment trial, the double-blind was not broken; both improved and unimproved subjects were randomized in a double-blind fashion to receive either full-cycle or half-cycle sertraline in the 3-month extension study. Results showed that the total premenstrual scores from the Penn Daily Symptom Report (DSR) were lower in the half-cycle dosing group in each of the 3 treatment months but did not differ with statistical significance from the full-cycle dosing group. Further analysis of the 17 DSR items showed that mood swings, nervous tension, feeling out of control, and confusion were significantly lower (p < 0.05) at endpoint in the half-cycle dosing group. Overall, subjects who improved in prior treatment remained improved; approximately half the subjects who were unimproved at entry into the extension study improved, regardless of the dosing regimen. The results add support to other preliminary reports of efficacy of serotonergic antidepressants administered premenstrually and indicate the clinical importance of determining an optimal dose/benefit ratio of serotonergic antidepressants for PMS patients.

Adolescent↗