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Biomedical subjects

Martin B Keller

Publications and source records attributed to Martin B Keller.

At least 19 recordsLinked to original sources
PubMed2026

Remission status in persistent depressive disorder following acute treatment with psychotherapy plus medication or medication alone: A 2-year naturalistic follow-up.

OBJECTIVE: Long-term benefits of acute-phase treatments for persistent depressive disorder (PDD) are unclear. Treatment guidelines disagree on the efficacy of cognitive behavioral analysis system of psychotherapy (CBASP). We examined whether acute CBASP protected against recurrence in PDD patients over two years of naturalistic follow-up. METHODS: An observational study evaluated major depressive episode (MDE) recurrences in patients completing the Research Evaluating the Value of Augmenting Medication with Psychotherapy (REVAMP) trial. Enrollees 18-75 years had PDD: current chronic MDE, recurrent MDEs with incomplete recovery, or double depression. All received open-label antidepressant medication (ADM) for 12 weeks. Non-remitters, continuing on ADM, were randomized (2:2:1) to 12 weeks of 1) CBASP, 2) brief supportive therapy (BSP), or 3) ADM alone (MEDS). Patients completing this 12-week randomized phase were offered two-year follow-up. Blinded raters assessed the primary outcome, remission status, using the Longitudinal Interval Follow-up Evaluation and Hamilton Depression Rating Scale at 3-month intervals. Analyses evaluated group differences and non-specific predictors of remission status. RESULTS: Of 323 participants entering follow-up, 203 (62.8%) met current MDE criteria during follow-up, without between-group differences: BSP: 83 (65.3%), CBASP: 85 (60.2%), MEDS: 35 (63.6%), Chi-square = 0.75; p = 0.69. Remission after acute treatment, lack of comorbid anxiety disorder, and female gender were significantly associated with lower recurrence risk. CONCLUSION: Similar to the acute phase outcomes, no group differences emerged over the 2-year follow-up, suggesting no long-term benefit of a 12-week CBASP treatment with ADM over other PDD treatments. Findings underscore the difficulty of PDD treatment and the importance of acute treatment remission. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00057551.

Antidepressant↗
PubMed2006

Psychometric characteristics of the Mobility Inventory in a longitudinal study of anxiety disorders: replicating and exploring a three component solution.

Psychometric characteristics of the Mobility Inventory (MI) were examined in 216 outpatients diagnosed with panic disorder with agoraphobia participating in a longitudinal study of anxiety disorders. An exploratory principal components analysis replicated a three-component solution for the MI reported in prior studies, with components corresponding to avoidance of public spaces, avoidance of enclosed spaces, and avoidance of open spaces. Correlational analyses suggested that the components tap unique but related areas of avoidance that were remarkably stable across periods of 1, 3, and 5 years between administrations. Implications of these results for future studies of agoraphobia are discussed.

Adult↗
PubMed2006

Effects of risperidone augmentation in patients with treatment-resistant depression: Results of open-label treatment followed by double-blind continuation.

Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in- and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with <50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17< or =7 or CGI-S < or = 2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had <50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (<25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p = 0.05); relapse rates were 56.1 and 64.1%, respectively (p < or = 0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.

Adolescent↗
PubMed2006

The distinct temperament profiles of bipolar I, bipolar II and unipolar patients.

BACKGROUND: Despite a plethora of studies, controversies abound on whether the long-term traits of unipolar and bipolar patients could be differentiated by temperament and whether these traits, in turn, could be distinguished from subthreshold affective symptomatology. METHODS: 98 bipolar I (BP-I), 64 bipolar II (BP-II), and 251 unipolar major depressive disorder (UP-MDD) patients all when recovered from discrete affective episodes) and 617 relatives, spouses or acquaintances without lifetime RDC diagnoses (the comparison group, CG) were administered a battery of 17 self-rated personality scales chosen for theoretical relevance to mood disorders. Subsamples of each of the four groups also received the General Behavior Inventory (GBI). RESULTS: Of the 436 personality items, 103 that significantly distinguished the three patient groups were subjected to principal components analysis, yielding four factors which reflect the temperamental dimensions of "Mood Lability", "Energy-Assertiveness," "Sensitivity-Brooding," and "Social Anxiety." Most BP-I described themselves as near normal in emotional stability and extroversion; BP-II emerged as labile in mood, energetic and assertive, yet sensitive and brooding; MDD were socially timid, sensitive and brooding. Gender and age did not have marked influence on these overall profiles. Within the MDD group, those with baseline dysthymia were the most pathological (i.e., high in neuroticism, insecurity and introversion). Selected GBI items measuring hypomania and biphasic mood changes were endorsed significantly more often by BP-II. Finally, it is relevant to highlight a methodologic finding about the precision these derived temperament factors brought to the UP-BP differentiation. Unlike BP-I who were low on neuroticism, both BP-II and UP scored high on this measure: yet, in the case of BP-II high neuroticism was largely due to mood lability, in UP it reflected subdepressive traits. LIMITATION: We used self-rated personality measures, a possible limitation generic to the paper-and-pencil personality literature. It is therefore likely that BP-I may have over-rated their "sanguinity"; or should one consider such self-report as a reliable reflection of one's temperament? One can raise similar unanswerable questions about "depressiveness" and "mood lability." CONCLUSION: As contrasted to CG and published norms, the postmorbid self-described "usual" personality is 1) sanguine among many, but not all, BP-I; 2) labile or cyclothymic among BP-II; and 3) subanxious and subdepressive among UP. It is further noteworthy that with the exception of BP-II, the temperament scores of BP-I and MDD were within one SD from published norms. Rather than being pathological, these attributes are best conceived as subclinical temperamental variants of the normal, thereby supporting the notion of continuity between interepisodic and episodic phases of affective disorders. These findings overall are in line with Kraepelin's views and contrary to the DSM-IV formulation of axis-II constructs as being pathological and sharply demarcated from affective episodes.

Adult↗
PubMed2006

Characteristics and predictors of full and partial recovery from generalized anxiety disorder in primary care patients.

The current study examined the naturalistic course of generalized anxiety disorder (GAD) in a sample of 113 primary care patients across a 2-year period. Initial diagnoses were established using structured clinical interviews according to DSM-IV diagnostic criteria. Results indicated that the majority of patients meeting DSM-IV diagnostic criteria for GAD were still symptomatic to some degree after 2 years of follow-up. Rates of full and partial recovery from GAD, however, were found to be higher than those reported for previous studies of GAD in psychiatric patients. Diagnostic comorbidity, severity of psychosocial impairment, and gender were found to be significantly associated with achieving full or partial recovery from GAD. Psychiatric treatment was not found to be associated with time to full or partial recovery from GAD symptoms, likely due to a treatment-biasing effect. These results underscore that GAD is a chronic and persistent illness in primary care patients.

Adult↗
PubMed2006

The naturalistic course of unipolar major depression in the absence of somatic therapy.

The goal of the study was to describe the naturalistic course of unipolar major depression in subjects not receiving somatic therapy for their depressive illness. Affectively ill individuals were recruited into the Collaborative Depression Study and followed prospectively for up to 15 years. One hundred thirty subjects who recovered from their intake episode of major depression subsequently experienced a recurrence that went untreated for at least 4 weeks following onset of the recurrence. The duration of the recurrent episode was examined using survival analytic techniques. Of the 130 subjects, 46 obtained somatic therapy at some time during the course of their depressive illness, while 84 subjects received no somatic therapy throughout their entire depressive episode. Survival analysis, which accounts for these 46 individuals by censoring their episodes at the time treatment was obtained, yielded a median time to recovery of 23 weeks. In the subsample of 84 subjects whose depressive illness went untreated from its inception through its resolution, the median time to recovery was 13 weeks. These results suggest that there is a high rate of recovery in individuals not receiving somatic treatment of their depressive illness, particularly in the first 3 months of an episode. Because treatment-seeking behavior is known to be associated with a worse prognosis, 23 weeks probably represents a lower-limit approximation of the median duration of an untreated depressive episode.

Adolescent↗
PubMed2006

Distinguishing bipolar major depression from unipolar major depression with the screening assessment of depression-polarity (SAD-P).

BACKGROUND: Patients with bipolar I or II major depression are often misdiagnosed with unipolar major depression. The goal of this study was to develop and validate a brief instrument to screen for bipolar disorder in patients actively ill with major depression. METHOD: The sample consisted of subjects who enrolled in the National Institute of Mental Health-Collaborative Program on the Psychobiology of Depression-Clinical Studies from 1978 to 1981 during an episode of major depression and included 91 subjects with bipolar I major depression, 52 with bipolar II major depression, and 338 with unipolar major depression diagnosed according to Research Diagnostic Criteria. Most of the subjects were inpatients at the time of enrollment, and subjects were prospectively followed for up to 20 years. In order to create, test, and cross-validate the screening instrument, a split-sample data analytic procedure was performed. This procedure yielded 3 groups of subjects: the bipolar I index sample, the bipolar I cross-validation sample, and the bipolar II cross-validation sample. Each group included subjects with bipolar major depression and subjects with unipolar major depression. Within the bipolar I index sample, subjects with bipolar I major depression at study intake were compared with subjects with unipolar major depression at study intake on a pool of 59 sociodemographic and clinical candidate variables. The 3 variables showing the greatest disparity between bipolar I subjects and unipolar subjects were selected for the screen, the Screening Assessment of Depression-Polarity (SAD-P). The operating characteristics of the SAD-P were then examined within the bipolar I index sample, bipolar I cross-validation sample, and bipolar II cross-validation sample. RESULTS: The items selected for the screening instrument were (1) presence of delusions during the current episode of major depression, (2) number of prior episodes of major depression, and (3) family history of major depression or mania. The screen identified bipolar major depression with a sensitivity of 0.82 in the bipolar I index sample, 0.72 in the bipolar I cross-validation sample, and 0.58 in the bipolar II cross-validation sample. With regard to misclassifying subjects with unipolar major depression, the screen provided a positive predictive value of 0.36 in the bipolar I index sample, 0.29 in the bipolar I cross-validation sample, and 0.27 in the bipolar II cross-validation sample. CONCLUSION: We suggest using the 3-item SAD-P as a preliminary screen for bipolar disorder in patients who present with an active episode of major depression.

Adult↗
PubMed2006

Prevalence and impact of comorbid anxiety and bipolar disorder.

Comorbid conditions pose a serious risk to patients with bipolar disorder, but anxiety comorbidity poses a specific hazard due to the increased negative impact of anxiety on illness course and treatment. Anxiety comorbidity appears to be highly prevalent and is associated with intensified symptoms of bipolar disorder and additional comorbid disorders, resulting in a negative impact on the patient and on the course of the illness. The presence of anxiety in bipolar patients is also associated with a lowered age at onset, hampered patient response to treatment such as lithium, increased rates of suicide and substance abuse, and decreased quality of life. Patients can experience work, family, and social impairment and be made to contend with increased health care costs and strains on family support. Studies are few and have a limited scope, and many have failed to consider the clinical significance of comorbid anxiety and bipolar disorder. Because the degree to which anxiety impacts patients with bipolar disorder is not fully known, more information is needed about the relationship between bipolar disorder and anxiety.

Adolescent↗
PubMed2006

Social anxiety disorder clinical course and outcome: review of Harvard/Brown Anxiety Research Project (HARP) findings.

Preliminary findings from a long-term, prospective, longitudinal, naturalistic treatment study of adults with social anxiety disorder (SAD) demonstrate that this illness has a chronic course and a greater adverse impact on social functioning than do depressive symptoms or chronic medical illnesses. Comorbid anxiety, depressive, and personality disorders are common in patients with SAD. Only 35% of patients with SAD recovered after 10 years of prospective follow-up. Whereas, the relapse rate, once recovery is achieved, is 34% during this 10-year follow-up. Treatment is underutilized in patients with SAD, and a long-term treatment approach may be needed to improve the likelihood of recovery from SAD.

Adult↗
PubMed2005

Assessing insomnia severity in depression: comparison of depression rating scales and sleep diaries.

Depression and sleep researchers typically assess insomnia severity differently. Whereas depression researchers usually assess insomnia with items on depression symptom inventories, sleep researchers usually assess the subjective experience of insomnia with sleep diaries. The present manuscript utilizes baseline data from 397 participants in a large multi-site chronic depression study to assess agreement between these two methodologies. The results indicate that the early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD(24)) and the Inventory of Depression Symptoms - Self Report (IDS-SR(30)) are highly correlated with the weekly mean values of time to sleep onset, time awake after sleep onset, and time awake prior to the planned wake-up obtained from prospective sleep diaries. Results also reveal significant correspondence between the weekly-mean of daily sleep efficiency, an accepted measure of sleep continuity (the ratio between reported time asleep and time in bed), and the insomnia scale scores of the HRSD(24) and the IDS-SR(30) (the mean score on the three insomnia items of each depression measure). Unit increments in HRSD(24) scores for early, middle and late insomnia were associated with significant increases in unwanted minutes awake for corresponding periods on sleep diaries. Similar relationships were found for early insomnia on the IDS-SR(30) but not for middle and late insomnia. Overall, with few exceptions, findings revealed substantial agreement between the HRSD(24), IDS-SR(30) and prospective sleep diary data. The study supports the validity of the sleep items and sleep subscales of the HRSD(24) and the IDS-SR(30) as global measures of insomnia severity in depression. Conventional sleep assessment procedures can complement depression scales by providing additional information about specific aspects of sleep in depression.

Adult↗
PubMed2005

Psychosocial disability in the course of bipolar I and II disorders: a prospective, comparative, longitudinal study.

CONTEXT: Evidence of psychosocial disability in bipolar disorder is based primarily on bipolar I disorder (BP-I) and does not relate disability to affective symptom severity and polarity or to bipolar II disorder (BP-II). OBJECTIVE: To provide detailed data on psychosocial disability in relation to symptom status during the long-term course of BP-I and BP-II. DESIGN: A naturalistic study with 20 years of prospective, systematic follow-up. SETTING: Inpatient and outpatient treatment facilities at 5 US academic centers. Patients One hundred fifty-eight patients with BP-I and 133 patients with BP-II who were followed up for a mean (SD) of 15 (4.8) years in the National Institute of Mental Health Collaborative Depression Study. MAIN OUTCOME MEASURES: The relationship, by random regression, between Range of Impaired Functioning Tool psychosocial impairment scores and affective symptom status in 1-month periods during the long-term course of illness from 6-month and yearly Longitudinal Interval Follow-up Evaluation interviews. RESULTS: Psychosocial impairment increases significantly with each increment in depressive symptom severity for BP-I and BP-II and with most increments in manic symptom severity for BP-I. Subsyndromal hypomanic symptoms are not disabling in BP-II, and they may even enhance functioning. Depressive symptoms are at least as disabling as manic or hypomanic symptoms at corresponding severity levels and, in some cases, significantly more so. At each level of depressive symptom severity, BP-I and BP-II are equally impairing. When asymptomatic, patients with bipolar disorder have good psychosocial functioning, although it is not as good as that of well controls. CONCLUSIONS: Psychosocial disability fluctuates in parallel with changes in affective symptom severity in BP-I and BP-II. Important findings for clinical management are the following: (1) depressive episodes and symptoms, which dominate the course of BP-I and BP-II, are equal to or more disabling than corresponding levels of manic or hypomanic symptoms; (2) subsyndromal depressive symptoms, but not subsyndromal manic or hypomanic symptoms, are associated with significant impairment; and (3) subsyndromal hypomanic symptoms appear to enhance functioning in BP-II.

Adaptation, Psychological↗
PubMed2005

Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not.

CONTEXT: Although various strategies are available to manage nonresponders to an initial treatment for depression, no controlled trials address the utility of switching from an antidepressant medication to psychotherapy or vice versa. OBJECTIVE: To compare the responses of chronically depressed nonresponders to 12 weeks of treatment with either nefazodone or cognitive behavioral analysis system of psychotherapy (CBASP) who were crossed over to the alternate treatment (nefazodone, n = 79; CBASP, n = 61). DESIGN: Crossover trial. SETTING: Twelve academic outpatient psychiatric centers. PATIENTS: There were 140 outpatients with chronic major depressive disorder; 92 (65.7%) were female, 126 (90.0%) were white, and the mean age was 43.1 years. Thirty participants dropped out of the study prematurely, 22 in the nefazodone group and 8 in the CBASP group. INTERVENTIONS: Treatment lasted 12 weeks. The dosage of nefazodone was 100 to 600 mg/d; CBASP was provided twice weekly during weeks 1 through 4 and weekly thereafter. MAIN OUTCOME MEASURES: The 24-item Hamilton Rating Scale for Depression, administered by raters blinded to treatment, the Clinician Global Impressions-Severity scale, and the 30-item Inventory for Depressive Symptomatology-Self-Report. RESULTS: Analysis of the intent-to-treat sample revealed that both the switch from nefazodone to CBASP and the switch from from CBASP to nefazodone resulted in clinically and statistically significant improvements in symptoms. Neither the rates of response nor the rates of remission were significantly different when the groups of completers were compared. However, the switch to CBASP following nefazodone therapy was associated with significantly less attrition due to adverse events, which may explain the higher intent-to-treat response rate among those crossed over to CBASP (57% vs 42%). CONCLUSIONS: Among chronically depressed individuals, CBASP appears to be efficacious for nonresponders to nefazodone, and nefazodone appears to be effective for CBASP nonresponders. A switch from an antidepressant medication to psychotherapy or vice versa appears to be useful for nonresponders to the initial treatment.

Adult↗
PubMed2005

Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in the treatment of generalized anxiety disorder and social phobia.

The past decade has brought major new developments in the psychopharmacologic management of generalized anxiety disorder and social phobia. We examined medication-prescribing patterns for the treatment of these anxiety disorders for 12 years to assess changes in patients' anti-anxiety psychotropic medication usage during that period of evolving practice guidelines. We examined psychotropic medication use in 305 patients with generalized anxiety disorder and 232 with social phobia enrolled in the Harvard/Brown Anxiety Disorders Research Project (HARP), a prospective, longitudinal study of anxiety disorders. Psychotropic treatment patterns seem to have remained relatively stable over 12 years with benzodiazepines the medications most commonly used for both generalized anxiety disorder and social phobia. Comparatively, selective serotonin reuptake inhibitor (SSRI) and venlafaxine usage as stand-alone medications for these disorders remained low throughout the follow-up period. At the 12-year follow-up, 24% of patients with generalized anxiety disorder and 30% of patients with social phobia were utilizing neither an SSRI/selective norepinephrine reuptake inhibitor (SNRI) nor a benzodiazepine. Treatment recommendations for use of SSRIs and venlafaxine in the management of generalized anxiety disorder and social phobia initially promulgated in 1998 had a modest impact on changes in psychopharmacologic practice 4-5 years later. Difficulties in the implementation of treatment guidelines are discussed.

Adult↗
PubMed2005

Comparing the effects of antidepressants: consensus guidelines for evaluating quantitative reviews of antidepressant efficacy.

With increasing numbers of treatment options available for patients with major depression over the last decade and the growing body of evidence describing their efficacy and safety, clinicians often find it difficult to determine the best and most appropriate evidence-based treatment for each patient. Systematic reviews utilizing statistical methods that synthesize and evaluate data from a number of studies have become increasingly more available over the past decade. We review major findings and lessons learned from salient examples of quantitative analyses of antidepressant research and provide recommendations for meta-analysts, journal and grant reviewers, and research 'consumers' (ie, clinicians) for conducting, reporting, and evaluating such analyses.

Antidepressive Agents↗
PubMed2005

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↗
PubMed2005

Long-term use of benzodiazepines in participants with comorbid anxiety and alcohol use disorders.

BACKGROUND: Although the only widely accepted role for benzodiazepines in alcohol dependence is the treatment of withdrawal syndromes, they are frequently prescribed outside of this clinical setting. There is little empirical evidence to guide the rational use of benzodiazepines in the common clinical situation where anxiety disorders are comorbid with alcohol use disorders (AUD). Since January 1989, the Harvard Anxiety Research Program has naturalistically monitored the prospective clinical course of people with anxiety disorders, some of whom had a history of AUD. Earlier research showed that the use of benzodiazepines was not significantly associated with the presence or absence of a history of an AUD over the first year of follow-up. This report extends that investigation. METHODS: Using standard parametric analytic methods, patterns of benzodiazepine use (routinely prescribed medication and as-needed [PRN] use) among participants receiving benzodiazepine treatment was prospectively examined over the course of 12 years. Differences in benzodiazepine usage patterns were examined in each year of follow-up between participants who did (n=120) and did not (n=425) have a new episode of AUD. Using proportional hazards regression analysis, benzodiazepine usage levels were examined as predictors of recovery and recurrence of AUD. Additionally, random-effects regression analyses were used to examine the patterns of benzodiazepine use before and after the onset of a prospectively observed episode of AUD. RESULTS: Benzodiazepine usage levels remained stable for the full sample over the course of the 12 years. Benzodiazepine use did not distinguish participants who had a new AUD from those who did not. Over the 12 years of follow-up, participants who had an AUD used more PRN medication in years five to eight. This difference reached statistical significance but was not clinically significant. Benzodiazepine usage levels did not predict recovery or recurrence in AUD subjects. Neither the total dose nor the PRN usage of benzodiazepines was significantly associated with the onset of AUD, but when combined into a measure of any benzodiazepine use, a relationship between increased use and the onset of AUD emerged. CONCLUSIONS: For participants in the Harvard Anxiety Research Program with comorbid alcohol dependence and anxiety disorders, there was little association between the use of benzodiazepines and the occurrence of a new AUD. Neither was there a temporal relationship between the use of benzodiazepines and the onset of a new AUD. Whether or not this finding extends to a broader patient population or a group of people who present to addictions treatment awaits further investigation.

Adult↗
PubMed2005

Relapse prevention with gepirone ER in outpatients with major depression.

To evaluate long-term efficacy and tolerability of the serotonin 5-HT1A receptor agonist, gepirone extended release (ER), a multicenter, randomized, placebo-controlled relapse prevention study was performed in patients with recurrent major depression (DSM-IV criteria). Patients 18 to 70 years, with a primary diagnosis of recurrent major depression (DSM-IV; 296.3) and a screening and baseline HAMD-17 total score >/=20 were eligible. After a 3- to 14-day (dependent on pretrial medication) single-blind placebo washout period, eligible patients entered an 8- or 12-week (depending on time to remission) open-label gepirone ER treatment period. They initially received a dose of 20 mg/d gepirone ER and were titrated to a dose of 40 to 80 mg/d. Patients who achieved remission (HAMD-17 total score </=8) were randomized to double-blind continuation of their gepirone ER treatment or placebo for 40 to 44 weeks. The primary end point was a comparison of the relapse rates between gepirone ER and placebo. Relapse was defined as a HAMD-17 total score >/=16 or discontinuation for lack of efficacy. A total of 420 patients were treated in the open-label phase. Of these, 303 (72.1%) completed the open-label phase and 250 (59.5%) fulfilled the criteria for remission and were randomized into the double-blind continuation phase (gepirone ER: n = 126; placebo: n = 124). The mean (+/-SD) final titrated dose of gepirone ER was 61.9 (+/-17.0) mg/d in the double-blind continuation phase. The relapse rate in the gepirone ER group was statistically significantly lower than that in the placebo group, 23.0% versus 34.7%, respectively (P = 0.024). During the open-label phase, adverse events that occurred in more than 5% of patients were nausea (15.7%), dizziness (13.1%), headache (12.9%), insomnia (6.2%), and vertigo (6.0%). During the continuation phase, the incidence of newly or re-emerging adverse events was similar with gepirone ER (43.7%) and placebo (42.7%). Adverse events different from those occurring during the open-label phase were not apparent. All adverse events occurred in less than 5% of patients with the exception of flu syndrome and headache. In conclusion, gepirone ER at a dose range of 40 to 80 mg/d is effective for relapse prevention in patients with recurrent major depression. It is well tolerated during long-term treatment for up to approximately one year.

Adult↗