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Alan J Gelenberg

Publications and source records attributed to Alan J Gelenberg.

At least 19 recordsLinked to original sources

Report by the ACNP Task Force on response and remission in major depressive disorder.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

Clinical Trials as Topic↗

Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial.

CONTEXT: In patients with diabetes mellitus, depression is a prevalent and recurrent problem that adversely affects the medical prognosis. OBJECTIVE: To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes. DESIGN: A randomized, double-blind, placebo-controlled, maintenance treatment trial. Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline (n = 79) or placebo (n = 73) and were followed up for up to 52 weeks or until depression recurred. SETTING: Outpatient clinics at Washington University, St Louis, MO, the University of Washington, Seattle, and the University of Arizona, Tucson. PATIENTS: One hundred fifty-two patients with diabetes (mean age, 52.8 years; 59.9% female; 82.9% with type 2 diabetes) who recovered from major depression (43.3% of those initially assigned) during 16 weeks of open-label treatment with sertraline (mean dose, 117.9 mg/d). INTERVENTION: Sertraline continued at recovery dose or identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was length of time (measured as the number of days after randomization) to recurrence of major depression as defined in DSM-IV. The secondary outcome was glycemic control, which was assessed via serial determinations of glycosylated hemoglobin levels. RESULTS: Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo (hazard ratio = 0.51; 95% confidence interval, 0.31-0.85; P = .02). Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline. Glycosylated hemoglobin levels decreased during the open treatment phase (mean +/- SD glycosylated hemoglobin level reduction, -0.4% +/- 1.4%; P = .002). Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance (P = .002) and did not differ between treatment groups (P = .90). CONCLUSIONS: In patients with diabetes, maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression. Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year.

Age of Onset↗

Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder.

BACKGROUND: Evidence indicates that venlafaxine hydrochloride extended release (ER) effectively ameliorates anxiety symptoms. OBJECTIVES: To evaluate the efficacy, safety, and tolerability of flexible-dose venlafaxine ER compared with placebo in the short-term treatment of generalized social anxiety disorder and, secondarily, to compare paroxetine with venlafaxine ER and paroxetine with placebo. DESIGN: Adult outpatients with DSM-IV generalized social anxiety disorder for 6 months or longer were randomly assigned to receive venlafaxine hydrochloride ER (75-225 mg/d), paroxetine (20-50 mg/d), or placebo for 12 weeks or less at 26 centers in the United States. The primary outcome measure was the total Liebowitz Social Anxiety Scale score. Secondary measures included response (Clinical Global Impression-Improvement score, 1 or 2) rates and Clinical Global Impression-Severity of Illness and Social Phobia Inventory scores. RESULTS: Of 440 patients treated, 413 (93.9%) were included in the last-observation-carried-forward efficacy analysis; of the 429 patients in the safety population, 318 (74.1%) completed the study. Mean daily doses were 201.7 mg (SD, 38.1 mg) of venlafaxine hydrochloride ER and 46.0 mg (SD, 7.9 mg) of paroxetine. Venlafaxine ER treatment was significantly superior to placebo at weeks 1 through 12 on the Liebowitz Social Anxiety Scale and Social Phobia Inventory and at week 2 and weeks 6 through 12 for Clinical Global Impression-Severity of Illness and responder status, and was significantly superior to paroxetine treatment at weeks 1 and 2 for the Social Phobia Inventory (P < .05 for all). Paroxetine treatment was significantly superior to placebo at weeks 3 through 12 on the Liebowitz Social Anxiety Scale, the Clinical Global Impression-Severity of Illness scale, and the Social Phobia Inventory, and at weeks 4 through 12 for response (P < .05 for all). Week 12 response rates were significantly greater for the venlafaxine ER and paroxetine groups (58.6% and 62.5%, respectively) vs the placebo group (36.1%) (P < .001 for both). CONCLUSION: Venlafaxine ER is effective in the short-term treatment of generalized social anxiety disorder, with efficacy and tolerability comparable to paroxetine.

Adult↗

Self-reported depressive symptom measures: sensitivity to detecting change in a randomized, controlled trial of chronically depressed, nonpsychotic outpatients.

This study evaluated and compared the performance of three self-report measures: (1) 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR30); (2) 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16); and (3) Patient Global Impression-Improvement (PGI-I) in assessing clinical outcomes in depressed patients during a 12-week, acute phase, randomized, controlled trial comparing nefazodone, cognitive-behavioral analysis system of psychotherapy (CBASP), and the combination in the treatment of chronic depression. The IDS-SR30, QIDS-SR16, PGI-I, and the 24-item Hamilton Depression Rating Scale (HDRS24) ratings were collected at baseline and at weeks 1-4, 6, 8, 10, and 12. Response was defined a priori as a > or =50% reduction in baseline total score for the IDS-SR30 or for the QIDS-SR16 or as a PGI-I score of 1 or 2 at exit. Overall response rates (LOCF) to nefazodone were 41% (IDS-SR30), 45% (QIDS-SR16), 53% (PCI-I), and 47% (HDRS17). For CBASP, response rates were 41% (IDS-SR30), 45% (QIDS-SR16), 48% (PGI-I), and 46% (HDRS17). For the combination, response rates were 68% (IDS-SR30 and QIDS-SR16), 73% (PGI-I), and 76% (HDRS17). Similarly, remission rates were comparable for nefazodone (IDS-SR30=32%, QIDS-SR16=28%, PGI-I=22%, HDRS17=30%), for CBASP (IDS-SR30=32%, QIDS-SR16=30%, PGI-I=21%, HDRS17=32%), and for the combination (IDS-SR30=52%, QIDS-SR16=50%, PGI-I=25%, HDRS17=49%). Both the IDS-SR30 and QIDS-SR16 closely mirrored and confirmed findings based on the HDRS24. These findings raise the possibility that these two self-reports could provide cost- and time-efficient substitutes for clinician ratings in treatment trials of outpatients with nonpsychotic MDD without cognitive impairment. Global patient ratings such as the PGI-I, as opposed to specific item-based ratings, provide less valid findings.

Adolescent↗

The effectiveness of generic agents in psychopharmacologic treatment.

In order to win FDA approval, generic drugs must demonstrate bioequivalence, namely the ability to achieve blood levels similar to those of the innovator ones on which they are based. They must have the same active ingredients, be identical in strength, dosage form, and route of administration, and be manufactured under strict FDA standards. Because basic efficacy and safety studies are not required, their cost is significantly lower. However, there can be important differences between the innovator drugs and generics, as well as among the generics themselves. More research needs to be done to establish true comparability.

Antipsychotic Agents↗

Trends in the use of antidepressants in a national sample of commercially insured pediatric patients, 1998 to 2002.

OBJECTIVE: The aim of this study was to estimate the prevalence of use of prescription antidepressants among children and adolescents by using nationwide data and to examine trends in use from 1998 to 2002. METHODS: Ambulatory prescription claims data for a nationwide random sample of more than 1.9 million life-years of commercially insured children (aged 18 years or younger) for the years 1998, 1999, 2000, 2001, and 2002 were examined retrospectively. The main outcome measure was trend in prevalence of antidepressant use. RESULTS: The overall prevalence of antidepressant use among children increased from 160 per 10000 (1.6 percent) in 1998 to 240 per 10000 (2.4 percent) in 2002, for an adjusted annual increase of 9.2 percent. The growth in the overall prevalence of antidepressant use was greater among girls (a 68 percent increase) than boys (a 34 percent increase). In 2002, antidepressant use was highest among girls aged 15 to 18 years, at 640 per 10000 (6.4 percent). The trend of increasing overall use of antidepressants among children and adolescents appears to have been driven primarily by greater use of selective serotonin reuptake inhibitors. CONCLUSIONS: The growth in the prevalence of use of antidepressant medications among youths appears to be continuing, and the rate of increase between 1998 and 2002 is similar to the rate of increase seen in the period of the second-generation antidepressants (late 1980s to mid-1990s).

Adolescent↗

The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication.

BACKGROUND: A continuation study of an extract of St. John's wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John's wort extract and placebo. METHOD: Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John's wort extract in the acute-phase study (phase 1) were continued on double-blind treatment with the same preparation for 24 weeks. Ninety-five subjects who did not respond to either St. John's wort or placebo were treated with an antidepressant for 24 weeks. RESULTS: During antidepressant treatment, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p <.0001), with no significant difference between St. John's wort nonresponders and placebo nonresponders. Of the 17 subjects continued on treatment with St. John's wort extract, 5 (29.4%) relapsed. CONCLUSIONS: The subjects who did not respond to St. John's wort extract or placebo in phase 1 were, by and large, not resistant to antidepressant treatment. This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects.

Adult↗

Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression.

BACKGROUND: Maintenance treatment to prevent recurrences is recommended for chronic forms of major depressive disorder (MDD), but few studies have examined maintenance efficacy of antidepressants with chronic MDD. This randomized, placebo-controlled study of the efficacy and safety of nefazodone in preventing recurrence was conducted for patients with chronic MDD. METHODS: A total of 165 outpatients with chronic, nonpsychotic MDD, MDD plus dysthymic disorder ("double-depression"), or recurrent MDD with incomplete inter-episode recovery, who achieved and maintained a clinical response during acute and continuation treatment with either nefazodone alone or nefazodone combined with psychotherapy, were randomized to 52 weeks of double-blind nefazodone (maximum dose 600 mg/day) or placebo. The occurrence of major depressive episodes during maintenance treatment was assessed with the 24-item Hamilton Rating Scale for Depression, a DSM-IV MDD checklist, and a blinded review of symptom exacerbations by a consensus committee of research clinicians. RESULTS: Application of a competing-risk model that estimated the conditional probability of recurrence among those patients remaining on active therapy revealed a significant (p =.043) difference between nefazodone (n = 76) and placebo (n = 74) when the latter part of the 1-year maintenance period was emphasized. At the end of 1 year, the conditional probability of recurrence was 30.3% for nefazodone-treated patients, compared with 47.5% for placebo-treated patients. Prior concomitant psychotherapy during acute/continuation treatment, although enhancing the initial response, was not associated with lower recurrence rates. Discontinuations due to adverse events were relatively low for both nefazodone (5.3%) and placebo (4.8%). Somnolence was significantly greater among the patients taking active medication (15.4%), compared with placebo (4.6%). CONCLUSIONS: Nefazodone is well-tolerated and is an effective maintenance therapy for chronic forms of MDD.

Acute Disease↗

Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.

CONTEXT: Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. OBJECTIVE: To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. DESIGN, SETTING, AND PATIENTS: Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. INTERVENTION: Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). RESULTS: Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration. CONCLUSION: In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.

Adult↗

Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder.

OBJECTIVES: The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well. METHODS: Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches. RESULTS: Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed. CONCLUSIONS: Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

Acetates↗

Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression.

BACKGROUND: Although various strategies have been proposed to treat antidepressant nonresponders, little controlled research has been published that examines prospectively the use of switching to an alternate antidepressant. METHODS: This was a multisite study in which outpatients with chronic major depression (with or without concurrent dysthymia), who failed to respond to 12 weeks of double-blind treatment with either sertraline hydrochloride (n = 117) or imipramine hydrochloride (n = 51), were crossed over or switched to 12 additional weeks of double-blind treatment with the alternate medication. Outcome measures included the 24-item Hamilton Rating Scale for Depression and the Clinical Global Impressions--Severity and Improvement scales. RESULTS: The switch from sertraline to imipramine (mean dosage, 221 mg/d) and from imipramine to sertraline (mean dosage, 163 mg/d) resulted in clinically and statistically significant improvements. The switch to sertraline treatment was associated with fewer adverse effect complaints and significantly less attrition owing to adverse effects. Although sertraline treatment also resulted in significantly higher response rates in the intent-to-treat samples (60% in the sertraline group and 44% in the imipramine group), neither the intent-to-treat remission rates nor the response and remission rates among study completers differed significantly. Moreover, after considering the effect of attrition, there were no significant treatment effects on the more comprehensive generalized estimating equation analyses of the continuous dependent measures. CONCLUSIONS: More than 50% of chronically depressed antidepressant nonresponders benefited from a switch from imipramine to sertraline, or vice versa, despite a high degree of chronicity. As in the initial trial, sertraline was generally better tolerated than imipramine. Switching to a standard antidepressant of a different class is a useful treatment strategy for antidepressant nonresponders and could be considered a standard of comparison for future studies of novel alternate strategies.

Adult↗

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Clinical Trials as Topic↗