Biomedical subjects

P R Houck

Publications and source records attributed to P R Houck.

At least 19 recordsLinked to original sources

PubMed1999

Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years.

CONTEXT: Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability. OBJECTIVE: To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years. DESIGN: A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist. SETTING: University-based psychiatric research clinic. PATIENTS: Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions. INTERVENTIONS: Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22). MAIN OUTCOME MEASURE: Recurrence of major depressive episode. RESULTS: The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years. CONCLUSION: In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.

Adrenergic Uptake Inhibitors↗

PubMed1999

Residual analysis in random regressions using SAS and S-PLUS.

A program package RRAP: Random Regression Residual Analysis Program using SAS [1] and S-PLUS [2] is available for performing random regression residual analysis. The PROCEDURE MIXED from SAS is used for statistical inference. Both elementary-level and individual-level residuals are used. The S-PLUS programs provide: (1) a transformation to orthogonalize the elementary-level correlated residuals for standard regression residual analyses; and (2) several statistics and plots for checking model assumptions, assessing model fitting and detecting outlying individuals. RRRAP starts with a SAS Macro RRRAPMAC on the data followed by a S-PLUS Program DoRRRAP on a UNIX system.

Models, Statistical↗

PubMed1999

Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy.

OBJECTIVE: The authors tested the hypothesis that nortriptyline and interpersonal psychotherapy, alone and in combination, are superior to placebo in achieving remission of bereavement-related major depressive episodes. METHOD: Eighty subjects, aged 50 years and older, with major depressive episodes that began within 6 months before or 12 months after the loss of a spouse or significant other were randomly assigned to a 16-week doubleblind trial of one of four treatment conditions: nortriptyline plus interpersonal psychotherapy (N = 16), nortriptyline alone in a medication clinic (N = 25), placebo plus interpersonal psychotherapy (N = 17), or placebo alone in a medication clinic (N = 22). The protocol required that the acute-phase double-blind treatment be ended after 8 weeks if Hamilton depression scale ratings had not improved by 50%. Remission was defined as a 17-item Hamilton scale score of 7 or lower for 3 consecutive weeks. RESULTS: The rate of remission for nortriptyline plus interpersonal psychotherapy was 69% (N = 11); for medication clinic, nortriptyline, 56% (N = 14); for placebo plus interpersonal psychotherapy, 29% (N = 5); and for medication clinic, placebo, 45% (N = 10). In a generalized logit model, there was a significant effect of nortriptyline over placebo but no interpersonal psychotherapy effect and no nortriptyline-by-interpersonal psychotherapy interaction. Rates of all-cause attrition were lowest in the nortriptyline plus interpersonal psychotherapy group. CONCLUSIONS: Nortriptyline was superior to placebo in achieving remission of bereavement-related major depressive episodes. The combination of medication and psychotherapy was associated with the highest rate of treatment completion. These results support the use of pharmacologic treatment of major depressive episodes in the wake of a serious life stressor such as bereavement.

Aged↗

PubMed1999

EEG sleep measures in later-life bereavement depression. A randomized, double-blind, placebo-controlled evaluation of nortriptyline.

The authors examined 1) effects of nortriptyline (NT) on electroencephalographic (EEG) sleep measures in elderly patients with bereavement-related depression in remission under randomized, double-blind, placebo-controlled conditions, and 2) the effects of clinical remission on sleep after discontinuation of medication. Subjects were classified as responders to placebo (n = 9) or NT (n = 18) and had EEG sleep studies at three time-points: before treatment (T1), remitted on medication or placebo (T2), and remitted off medication or placebo (T3). As compared with placebo, NT was differentially associated with decreases in REM sleep time and percent and increases in REM sleep density (T2). No changes in EEG sleep measures occurred in placebo responders. REM sleep measures in NT responders reverted to T1 levels after T3, with persistence of robust clinical remission and normal subjective sleep quality. These data suggest that NT alters REM sleep, but that EEG sleep characteristics in bereavement-related depression persist into remission.

Aged↗

PubMed1999

Treatment of 70(+)-year-olds with recurrent major depression. Excellent short-term but brittle long-term response.

The authors compared response rates, by age (60-69 vs. 70+), to acute, continuation, and 1-year maintenance depression treatment. Patients (N = 180) received open combined treatment with nortriptyline (NT)/placebo and interpersonal psychotherapy (IPT). Patients who recovered then entered randomized, double-blind maintenance treatment with NT or placebo or received maintenance monthly IPT (combined with NT or placebo). Comparison of time-to-remission and recovery and absolute rates of remission, relapse, recovery, and recurrence yielded similar times to/rates of remission and recovery; however, older patients had far more recurrence during the first year of maintenance therapy. Although responses to acute and continuation treatment with combined NT and psychotherapy were similar, the older group had more recurrence in the first year of maintenance. Continuation of combined medication and psychotherapy may represent the best long-term treatment.

Age Factors↗

PubMed1998

Latent structure of EEG sleep variables in depressed and control subjects: descriptions and clinical correlates.

In this study, we aimed to determine the latent structure of multiple EEG sleep variables in patients with major depressive disorder (MDD) and in healthy control subjects and to examine associations between sleep factors and clinical variables. Subjects included 109 women with MDD and 54 healthy control women. EEG sleep data were collected prior to any treatment. Principal components analysis (PCA) was conducted on a set of 24 sleep variables. Separate PCAs were run for patients with MDD, control subjects, and a matched group of patients and controls. Other analyses included correlations, t-tests and MANOVA. Each PCA identified four sleep factors that explained 70% of the total variance in individual sleep variables: slow wave sleep, REM sleep, sleep continuity and REM latency/delta sleep ratio (RL/DSR). Patients with MDD and healthy controls differed on the mean value of the sleep continuity factor, and a multivariate analysis of variance based on the PCA identified MDD-control differences in REM sleep and sleep continuity. In the MDD group, slow wave sleep correlated inversely with age and personality disorder symptoms; sleep continuity correlated with subjective sleep quality and anxiety; and RL/DSR correlated inversely with age. The mean value of the REM factor was higher among treatment non-responders than responders. EEG sleep variables have a similar latent structure in women with MDD and in healthy controls. These sleep factors are supported conceptually and empirically, and correlate with clinical measures in women with MDD. Multivariate statistical techniques decrease the risk of Type I and Type II errors when using a large number of collinear sleep measures, and can clarify conceptual issues related to sleep and depression.

Adult↗

PubMed1998

Characteristics and course of major depression in older primary care patients.

OBJECTIVE: Identify the morbidity patterns displayed by older primary care patients experiencing depressive symptomatology who do and do not meet criteria for a major depression. METHOD: Patients ages sixty and older presenting at two ambulatory internal medicine centers were administered the CES-D. Among those scoring > or = 11, 104 completed a comprehensive assessment of their psychiatric symptomatology, medical illness, and functional abilities. The assessment battery was again administered six months later. RESULTS: The point prevalence of major depression in older primary care patients is estimated at 9 percent based on SCID interviews. Patients meeting criteria for this diagnosis compared to those who are symptomatic but not experiencing a major depression described more extensive psychopathology but also significantly more limitations in performing social and functional roles. At six-month follow-up, only 11.5 percent of those initially diagnosed with a major depression were considered fully recovered. CONCLUSIONS: Major depression is a prevalent disorder in older primary care patients which affects their ability to perform expected social and physical roles. Mechanisms for delivering efficacious treatments in routine medical practice are of a high priority.

Age Factors↗

PubMed1998

A post hoc comparison of paroxetine and nortriptyline for symptoms of traumatic grief.

BACKGROUND: This report presents the results of an open-trial pilot study of paroxetine for symptoms of traumatic grief, compared with the effects of nortriptyline in an archival contrast group. METHOD: Data are presented on 15 subjects (4 men, 11 women), ranging in age from 40 to 79 years (mean age = 57 years), who experienced the loss of a spouse (N = 8), child (N =5), grandchild (N = 1), or parent (N = 1). Subjects were required to have a baseline score on the Inventory of Complicated Grief (ICG) of > or = 20. Treatment with paroxetine began at a median of 17 months (range, 6-139 months) after the loss. Paroxetine-treated subjects received a psychotherapy tailored for traumatic grief. Depressive symptoms were assessed by using the Hamilton Rating Scale for Depression (HAM-D). The ICG and the HAM-D were administered weekly over 4 months of paroxetine treatment (median dose = 30 mg/day). The group receiving paroxetine were then compared with a group (N = 22) participating in a separate trial of nortriptyline (median dose = 77.5 mg/day) for treatment of bereavement-related major depressive episodes. RESULTS: Level of traumatic grief symptoms (ICG) decreased by 53%, and depression ratings (HAM-D) decreased by 54% in paroxetine-treated subjects. Nortriptyline showed clinical effects comparable to those of paroxetine. CONCLUSION: Paroxetine may be an effective agent in the treatment of traumatic grief symptoms. A comparison of the paroxetine-treated group with a nortriptyline-treated group suggests that both agents have comparably beneficial effects on the symptoms of traumatic grief (as well as those of depression). However, the higher rate of diagnostic comorbidity in the paroxetine-treated group, together with the greater chronicity of their symptoms and the greater safety of paroxetine in overdose, leads us to favor paroxetine over nortriptyline for traumatic grief symptoms in general psychiatric practice. Further controlled evaluation of paroxetine for traumatic grief is necessary.

Adjustment Disorders↗

PubMed1998

Long-term ECG changes in depressed elderly patients treated with nortriptyline. A double-blind, randomized, placebo-controlled evaluation.

ECGs of 50 patients who completed a long-term nortriptyline (NT) study are presented at baseline, after 7 weeks on NT, and after 1 year. The ECGs of patients with preexisting cardiac disease were compared with non-cardiac patients. Significant ECG changes and increases in heart rate were observed by Week 7 and persisted at a mean of 55 weeks (range: 24-111) in patients who were continued on NT. No significant difference was found in long-term ECG effects in patients with preexisting cardiac disease; ECG changes reverted to baseline when placebo was substituted. Patients with known cardiac disease did not show significantly worse ECG changes on NT than non-cardiac patients.

Age Factors↗

PubMed1997

Maintenance nortriptyline effects on electroencephalographic sleep in elderly patients with recurrent major depression: double-blind, placebo- and plasma-level-controlled evaluation.

Our aim was to contrast the effects of maintenance nortriptyline and placebo on electroencephalographic sleep measures in elderly recurrent depressives who survived 1-year without recurrence of depression. Patients on nortriptyline took longer to fall asleep and did not maintain sleep better than patients on placebo; however, maintenance nortriptyline was associated with more delta-wave production and higher delta-wave density in the first non-REM (NREM) period relative to the second. Nortriptyline levels were positively but weakly related to all-night delta-wave production during maintenance (accounting for 6.6% of the variance in delta-wave counts). Total phasic REM activity increased 100% under chronic nortriptyline relative to placebo, with a robust increase in the rate of REM activity generation across the night. Effective long-term pharmacotherapy of recurrent major depression is associated with enhancement in the rate of delta-wave production in the first NREM period (i.e., delta sleep ratio) and of REM activity throughout the night.

Aged↗

PubMed1997

Sleep in the wake of complicated grief symptoms: an exploratory study.

Our aim was to explore the concept that the symptoms of complicated grief may be a form of posttraumatic distress, rather than depression, and thus may have different effects on sleep. Sixty-five recently bereaved elders with varying levels of symptoms of complicated grief and depression were stratified by high versus low levels of symptoms; a two-way analysis of variance examined main effects of level of complicated grief symptoms and depressive symptoms on selected sleep measures, as well as interactions. Complicated grief symptoms were independently associated with mild subjective sleep impairment but showed no main effects on electroencephalographic (EEG) sleep measures. In a multiple regression analysis, complicated grief symptoms interacted with depressive symptoms to increase REM sleep percent. Thus, it appears that complicated grief symptoms do not entail the changes of EEG sleep physiology seen in depression, with the possible exception of an interaction with coexisting depression to enhance REM sleep percent.

Aged↗

PubMed1997

Temporal profiles of the course of depression during treatment. Predictors of pathways toward recovery in the elderly.

BACKGROUND: Predictors of treatment response and recovery from depression in late life remain poorly understood. Previous studies have focused on a narrow range of response and recovery variables; namely, whether patients achieve or do not achieve a defined outcome or time to achieve the outcome. Whether patients vary in their pathways toward those outcomes--and the extent to which such variation can be anticipated by patient characteristics prior to treatment--has not been empirically examined. METHODS: Depression symptom levels were monitored for 18 weeks in 95 persons aged 60 years or older who were experiencing a recurrence of major depression. Subjects received standardized combined nortriptyline treatment and interpersonal psychotherapy throughout the period. Cluster analysis was used to identify depression recovery patterns. Multivariate analyses considered whether recovery patterns were predicted by pretreatment psychosocial, clinical, and electroencephalographic sleep characteristics. RESULTS: Four subgroups of elders were identified who differed in rate, stability, and direction of recovery, ie, those showing (1) rapid sustained improvement, (2) delayed but sustained improvement, (3) partial or mixed response, or (4) no response. Pretreatment characteristics reliably predicted subjects' group membership. Higher levels of acute and chronic stressors, poorer social supports, younger age at first depressive episode, endogenous depression, higher current anxiety, older current age, and poorer subjective and objective (electroencephalographic) sleep predicted poorer response profiles. CONCLUSIONS: There are multiple pathways by which individuals begin to emerge from depression; these pathways can be identified empirically. Variables from diverse psychobiologic domains can be used to predict which persons are likely to advance along which trajectories toward recovery.

Age Factors↗

PubMed1997

Clinical factors contributing to the differential diagnosis of primary insomnia and insomnia related to mental disorders.

OBJECTIVE: Primary insomnia and insomnia related to mental disorders are the two most common DSM-IV insomnia diagnoses, but distinguishing between them is difficult in clinical practice. This analysis was performed to identify clinical factors used by sleep specialists to distinguish primary insomnia from insomnia related to mental disorders. METHOD: Clinicians evaluated 216 patients referred for insomnia at five clinical sites, rated a list of clinical factors judged to contribute to each patient's presentation, and assigned diagnoses. Analysis of variance was performed, with contributing factors as the dependent variable and diagnostic group and clinic location as independent variables. RESULTS: Sleep specialists rated a psychiatric disorder as a stronger factor for insomnia related to mental disorders and rated negative conditioning and sleep hygiene as stronger factors for primary insomnia. However, a psychiatric disorder was rated as a contributing factor for 77% of patients who received a first diagnosis of primary insomnia. CONCLUSIONS: While neither sleep hygiene nor negative conditioning is a diagnostic criterion in DSM-IV, these results support the face validity of these clinical factors distinguishing between primary insomnia and insomnia related to mental disorders. The use of a psychiatric disorder as an inclusion criterion for insomnia related to mental disorders and an exclusion criterion for primary insomnia reinforces a categorical distinction between the two diagnoses, but the contribution of psychiatric symptoms in primary insomnia appears to be a clinically relevant one. These findings suggest the need for studies on the validity of negative conditioning and sleep hygiene in the etiology of primary insomnia, as well as on the significance of psychiatric disorders, especially depression, in primary insomnia.

Adolescent↗

PubMed1997

Which elderly patients with remitted depression remain well with continued interpersonal psychotherapy after discontinuation of antidepressant medication?

OBJECTIVE: This study was conducted to identify which elderly patients with remitted recurrent major depression remain well with maintenance interpersonal psychotherapy after discontinuation of active antidepressant medication (nortriptyline). METHOD: The authors examined outcomes of maintenance therapy over 1 year for 47 elderly patients who were randomly assigned to monthly maintenance interpersonal psychotherapy with placebo (N = 19) or to placebo and a supportive medication clinic without interpersonal psychotherapy (N = 28). A Kaplan-Meier survival analysis was performed on the basis of treatment assignment and subjective sleep quality assessed by the Pittsburgh Sleep Quality Index, on which good subjective sleep quality is indicated by a score of 5 or lower. RESULTS: Nine (90%) of 10 patients reporting good subjective sleep quality (by 1 month into continuation treatment) remained well for at least 1 year when treated with monthly maintenance interpersonal psychotherapy, versus five (31%) of 16 patients with good sleep quality assigned to a medication clinic, three (33%) of nine patients with impaired sleep quality treated with maintenance interpersonal psychotherapy, and two (17%) of 12 patients with impaired sleep quality assigned to a medication clinic. CONCLUSIONS: Recovery of good subjective sleep quality by early continuation treatment is useful in identifying which remitted elderly depressed patients will remain well with monthly maintenance interpersonal psychotherapy, following discontinuation of antidepressant medication, and which patients may be more vulnerable to recurrence of major depressive episodes in the absence of antidepressant medication.

Amitriptyline↗

PubMed1997

Differences over the life span in daily life-style regularity.

A diary-based instrument-the Social Rhythm Metric (SRM)-was used to assess the level of stability of daily social and behavioral rhythms in a group of 239 healthy subjects (112 male, 127 female) ranging in age from 20 to 89 years. Each subject completed the instrument for two consecutive weeks, which were averaged to yield one measure (SRM score) of life-style regularity [range 0 (least regular) to 7 (most regular)] and another of activity level index (ALI), corresponding to the number of (diary listed) activities done per week (max. = 119). SRM score increased reliably with age group at an average rate of 0.018 units per year. ALI showed an "inverted U"-shaped function with a maximum at about 50 years. SRM changes appeared not to be related to demographic differences between the age groups, although ALI differences may have been so related. No main effects or interactions were found with gender. Life-style regularity appears to increase over the life span in response to both biological and psychosocial changes and may represent an adaptation to age-related changes in the circadian system's sensitivity to entraining agents. Regular behavioral rhythms may be conducive to continued good health and well-being.

Activities of Daily Living↗

PubMed1997

Does lorazepam impair the antidepressant response to nortriptyline and psychotherapy?

BACKGROUND: This analysis sought to determine whether lorazepam influences time to response or rate of response in elderly depressed patients receiving nortriptyline and psychotherapy and to examine clinical and polysomnographic correlates of lorazepam treatment. METHOD: Patients with recurrent major depressive disorder (N = 119; mean +/- SD age = 68.0 +/- 6.1 years; diagnosis defined by Research Diagnostic Criteria) received acute treatment with nortriptyline and interpersonal psychotherapy. Thirty-five patients received open-label adjunctive lorazepam for anxiety or insomnia symptoms (LZ+) and 84 did not. Statistical analyses were conducted between the LZ+ group and a group of 35 patients who received no lorazepam (LZ-) and were matched for anxiety level. Patients had polysomnographic studies prior to treatment and after remission of depressive symptoms. RESULTS: The LZ+ group reported more anxiety on the Brief Symptom Inventory (p = .04) compared with the remaining 84 patients. The LZ+ group had a greater proportion of endogenous depression subtype than the anxiety-matched LZ- group, in addition to more abnormal EEG sleep (higher percentage of REM sleep, shorter REM latency, lower delta sleep ratio). Mean time to initial antidepressant response was no different between groups. However, a significantly greater proportion of LZ+ than LZ- patients responded to acute treatment (91.4% vs. 71.4%; p < .03). CONCLUSION: Adjunctive lorazepam does not slow the antidepressant response to combined antidepressant/psychotherapy treatment in elderly depressed patients, and it is associated with a greater likelihood of antidepressant response. A greater percentage of patients treated with lorazepam have endogenous depression subtype and abnormal sleep findings (EEG) than those who are not treated with lorazepam. Adjunctive lorazepam is useful for treating anxiety in elderly depressed patients.

Age Factors↗

PubMed1997

Accelerating response in geriatric depression: a pilot study combining sleep deprivation and paroxetine.

Elderly depressed patients often require an average of 12 weeks of pharmacotherapy before attaining remission. The delay between treatment initiation and remission may decrease compliance and prolongs suffering; hence, interventions that decrease the time to onset of antidepressant activity are needed. Our objective was to evaluate, in an open trial, the use of one night of total sleep deprivation combined with paroxetine to accelerate antidepressant response in elderly patients. Thirteen elderly patients with major depression were sleep-deprived for one night and started paroxetine on the night of recovery sleep. Patients were followed for twelve weeks, and clinical improvement was rated using the 17-item Hamilton Depression Rating Scale and a version of the Hamilton modified for sleep deprivation studies. 8/13 (62%) patients experienced significant improvement of depressive symptoms by 2 weeks. Within 12 weeks 11/13 (85%) patients responded to the combination of sleep deprivation and paroxetine. Median response time was 2 weeks. Clinical response at 12 weeks was correlated with changes in Sleep Deprivation Depression Rating Scale Scores between baseline and recovery sleep. In an open trial, the combined use of total sleep deprivation and paroxetine appears to be an effective method for speeding the onset of clinical antidepressant activity in geriatric depression and for improving early recognition of non-response.

Aged↗

PubMed1996

Quality of life in elderly patients with recurrent major depression: a factor analysis of the General Life Functioning Scale.

Quality of life profiles measured by the General Life Functioning (GLF) Scale were examined in elderly patients with recurrent major depression, before and during combined treatment with nortriptyline and interpersonal psychotherapy. The study group included 110 patients, 91 recovered and 19 nonrecovered, aged 60 to 80 years, suffering from at least their second lifetime episode of major depression. Repeated measures analysis of covariance (with Hamilton and Beck depression scores as time-dependent covariates) was used to compare the temporal course of overall GLF scores for the recovered and the nonrecovered groups. Factor analysis was used to examine whether the GLF Scale yielded an overall score and measured specific aspects of well-being and coping. There were significant differences in the overall GLF scores between recovered and nonrecovered patients, with the differences increasing from week 8 of treatment onward. Analysis revealed significant improvements in quality of life, as measured by overall GLF scores, over the course of treatment in both recovered and nonrecovered patients. Even when changes in Hamilton and Beck depression ratings were controlled for in the statistical analysis, improvements in GLF scores were found to be greater in recovered than in nonrecovered patients. Thus, the GLF measures more than change in level of depression. Its overall score also has high internal reliability.

Adaptation, Psychological↗