Treatment of men with major depression: a comparison of sequential cohorts treated with either cognitive-behavioral therapy or newer generation antidepressants.

OBJECTIVE: This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy in sequential cohorts of men with DSM-III-R major depression. METHOD: Patients were enrolled in consecutive standardized 16-week treatment protocols conducted in the same research clinic. The first group (N = 52) was treated with Beck's model of CBT, whereas the second group (N = 23) received randomized but open-label treatment with either fluoxetine (N = 10) or bupropion (N = 13). Crossover to the alternate medication was permitted after 8 weeks of treatment for antidepressant nonresponders. The patient groups were well matched prior to treatment. Outcomes included remission and nonresponse rates, as well as both independent clinical evaluations and self-reported measures of depressive symptoms. RESULTS: Despite limited statistical power to detect differences between treatments, depressed men treated with pharmacotherapy had significantly greater improvements on 4 of 6 continuous dependent measures and a significantly lower rate of nonresponse (i.e., 13% vs. 46%). The difference favoring pharmacotherapy was late-emerging and partially explained by crossing over nonresponders to the alternate medication. The advantage of pharmacotherapy over CBT also tended to be larger among the subgroup of patients with chronic depression. CONCLUSION: Results of prior research comparing pharmacotherapy and CBT may have been influenced by the composition of study groups, particularly the gender composition, the choice of antidepressant comparators, or an interaction of these factors. Prospective studies utilizing flexible dosing of modern antidepressants and, if necessary, sequential trials of dissimilar medications are needed to confirm these findings.

Is cognitive behavior therapy just a 'nonspecific' intervention for depression? A retrospective comparison of consecutive cohorts treated with cognitive behavior therapy or supportive counseling and pill placebo.

BACKGROUND: There is a dearth of placebo-controlled studies of cognitive behavior therapy (CBT) of depression and the largest such study, by Elkin et al. (Arch. Gen. Psychiatry 46 (1989) 971-982), failed to find a significant difference between CBT and a clinical management plus placebo condition. METHODS: The outcomes of two consecutive cohorts of out-patients with major depressive disorder, treated with either CBT (n=90) or a nonspecific control condition (support-counseling-placebo; SCP: n=100), were compared. Although the principal comparisons between the CBT and SCP conditions were delimited to the first 4 weeks of treatment, a secondary set of analyses addressed the subset of 16 patients who received 12 additional weeks of supportive therapy. RESULTS: A consistent pattern of statistically and clinically significant differences favoring CBT over SCP was found in both weeks 4 and 16. LIMITATIONS: Interpretation of these findings are subject to several potential confounds, including the non-randomized nature of the groups and the greater amount of therapeutic contact during the first 4 weeks of CBT. CONCLUSIONS: While these results do not lessen the need for additional prospective studies, our findings do suggest that CBT has therapeutic effects beyond those attributable to placebo-expectancy and other nonspecific factors.

Electroencephalographic sleep profiles before and after cognitive behavior therapy of depression.

BACKGROUND: Previous studies have not fully resolved the state-dependent vs traitlike behavior of the electroencephalographic sleep abnormalities associated with depression. We therefore examined the sleep profiles of depressed patients before and after 16 weeks of treatment with cognitive behavior therapy to determine the stability or reversibility of selected abnormalities. METHODS: Seventy-eight unmedicated patients with major depressive disorder were stratified into abnormal and normal subgroups on the basis of pretreatment sleep study results. Two prospectively defined types of sleep variables were studied: those expected to be traitlike or state independent (type 1) and those predicted to be reversible or state dependent (type 2). RESULTS: The type 1 sleep disturbances (reduced rapid eye movement latency, decreased delta sleep ratio, and decreased slow wave sleep [in percentage]) were stable, as predicted, across time. A composite measure of type 2 disturbances (based on rapid eye movement latency, sleep efficiency, and rapid eye movement density) improved significantly, although a minority of patients in remission had persistent abnormalities. CONCLUSIONS: The electroencephalographic sleep correlates of depression can be disaggregated into state-independent and partially reversible subgroups. Persistent sleep disturbances in remitted patients may have ominous prognostic implications.

The relationship between preabuse factors and psychological symptomatology in sexually abused girls.

This study investigated the relationship between preabuse factors and psychological symptomatology in sexually abused girls. Ninety-four sexually abused girls, 89 clinical controls, and 75 normal controls comprised the subject population. All subjects were ages 6-12. Preabuse information was obtained with the Developmental, Psychiatric, and Medical History (DPM). Symptom measures included the Children's Depression Inventory (CDI), State-Trait Anxiety Inventory for Children (STAIC), Piers-Harris Children's Self-Concept Scale, and the Child Behavior Checklist (CBCL parent version). Results indicated that the sexually abused and clinical control groups had significantly more prior developmental and psychiatric problems and significantly more past stressors on the DPM than the normal control group. In addition, in examining the sexually abused group only, prior developmental and psychiatric problems were clearly associated with increased behavioral and emotional problems (CBCL), self-reported depressive symptoms (CDI), and lower self-esteem (Piers-Harris). Parallel results were found in the clinical control group, although correlations were higher in the sexual abuse group. Findings are interpreted to support the notion that there are a multitude of variables that may affect the psychological adjustment of sexually abused children, including preabuse and post-abuse factors and the trauma of the abusive experience itself.

Peripheral thermal responsivity to facial cooling during sleep.

A recently developed technique for examining thermal sensitivity during sleep was used to assess whether skin and core temperature responses to thermal stimulation were altered by sleep state. The technique was designed to probe thermal responsivity without altering core body temperature or inducing awakening. Twenty-seven young men and women were studied during a sleep deprivation night and a sleep night three nights later. Cold water stimulation of the face alternated with an equal period of rewarming across a 40-min cycle throughout the night. Skin temperature from the finger and rectal temperature were continuously assessed. Sleep continuity and architecture were largely uninfluenced by the thermal stimulation. Finger skin temperature decreased during cold facial stimulation in both sleep and waking states. Skin temperature changes during sleep were approximately one-fifth the magnitude of those during waking. Core temperature was minimally influenced. REM sleep was associated with a greater amplitude decrease in finger temperature than was non-REM (NREM) sleep. The results support the utility of the technique as a probe of thermal responsivity during sleep and suggest a reduction of thermal responsivity during sleep and, more tentatively, an altered responsivity during REM versus NREM sleep.

Rapid eye movement sleep deprivation in elderly patients with concurrent symptoms of depression and dementia.

Rapid eye movement (REM) sleep measures distinguish elderly patients with depression from those with dementia. The authors used a 2-night REM sleep deprivation (RSD) protocol to characterize patients with mixed symptoms of depression and dementia in comparison with patients with "pure" depression or dementia and healthy controls. Mixed-symptom patients resembled dementia patients in baseline sleep measures, but their large change in phasic REM activity following RSD suggests neurobiological similarities to depression. Mixed-symptom patients with stable cognitive impairment had greater REM sleep rebound than those with a more progressive dementing course. These results are consistent with previous neuropathological and neurochemical data.

The balance of positive and negative affects in major depression: a further test of the States of Mind model.

The States of Mind (SOM) model provided a framework for assessing the balance between self-reported positive and negative affects in a sample of 39 outpatients with major depression and 43 healthy control subjects. The SOM model proposes that healthy functioning is characterized by an optimal balance of positive (P) and negative (N) cognitions or affects (P/(P + N) approximately 0.63), and that psychopathology is marked by deviations from the optimal balance. Research thus far has focused on the functional significance of cognitive rather than affective balance. Within this framework, we hypothesized that patients in untreated episodes of major depression would balance their positive and negative affects at the same level where depressed patients in other studies have balanced their positive and negative cognitions--namely, at P/(P + N) approximately 0.37. Points and confidence interval (CI) estimation procedures yielded results (mean = 0.35, 95% CI = 0.30 - 0.40) consistent with this hypothesis in a sample of 39 depressed male outpatients. Correlational analysis indicated that affect balance is inversely related to symptom severity as measured by self-report (Beck) and clinician-rating (Hamilton) scales.

Daytime sleepiness in the healthy "old old": a comparison with young adults.

OBJECTIVE: To determine if excessive daytime sleepiness is an inevitable consequence of aging. METHODS: Daytime sleepiness was measured using Multiple Sleep Latency Tests (MSLT's) before and after a night of total sleep deprivation in a sample of 22 healthy men and women in their eighties and 29 men and women in their twenties. RESULTS: Young adults were somewhat sleepier than elders, as measured by rapidity of sleep onset during daytime nap recordings using the MSLT, and showed a higher incidence of REM sleep during naps. However, recovery from the effects of acute sleep loss was slower in the elderly, judging from the presence of more daytime sleepiness 2 days after a night of total sleep deprivation. Such persistent sleepiness was absent in the young adult control group. CONCLUSIONS: Healthy persons in late old age may have a level of daytime sleepiness no greater than, and perhaps even less than, that seen in healthy young adults.

Sleep, depression, and suicide.

In a retrospective study of the electroencephalographic (EEG) sleep of major depressives with and without a history of suicide attempts, suicide attempters had longer sleep latency, lower sleep efficiency, and fewer late-night delta wave counts than normal controls. Nonattempters, compared to attempters, had less rapid eye movement (REM) time and activity in period 2, but more delta wave counts in non-REM period 4. Although both attempters and nonattempters were like controls in regard to REM period 2, patients with suicide attempts had altered intranight temporal distribution of phasic REM activity, with increased REM activity (by both visual and automated scoring) in REM sleep period 2 (significant group x period interaction). These findings, which may be more traitlike or persistent than state-related, are discussed in the context of current theories on the role of serotonin in the regulation of sleep and in suicidal behavior.

Sleep stage physiology, mood, and vigilance responses to total sleep deprivation in healthy 80-year-olds and 20-year-olds.

Little is known about sleep and the effects of total sleep loss in the 'old old' (i.e., 80-year-olds). We investigated sleep, mood, and performance responses to acute sleep deprivation in healthy 80-year-olds (n = 10) and 20-year-olds (n = 14). The protocol consisted of three nights of baseline sleep, one night of total sleep deprivation, and two nights of recovery sleep. Mood and vigilance were tested using visual analog scales and a Mackworth clock procedure in the morning and evening of each study day. Daytime sleepiness was measured by five naps on the days following the third and sixth nights. Old subjects had lower sleep efficiency and less delta sleep than young subjects. However, sleep continuity and delta sleep were enhanced in both groups on the first recovery night, indicating that sleep changes in old subjects are at least partially reversible by this procedure. Surprisingly, young subjects had shorter daytime sleep latencies than the old, suggesting a greater unmet sleep need in the former group. Mood and performance were disturbed by sleep loss in both groups, but to a greater extent among the young. This suggests that acute total sleep loss is a more disruptive procedure for the young than for the old.

Nocturnal penile tumescence in healthy 20- to 59-year-olds: a revisit.

This report presents data on normative nocturnal penile tumescence (NPT), based on a study of 48 healthy men aged 20-59 years, without complaints of erectile dysfunction. In general, the current measures show good concordance with those reported by Karacan and colleagues in 1976. The effect of "pathology-free" aging (from age 20 to 59) on electrographic measures of NPT is relatively modest, accounting for 8.4-14.4% of the variance. Furthermore, no age effect on visual estimates of erectile fullness or on buckling force estimates of penile rigidity were present. Maximum buckling force and maximum erectile fullness showed stability across the four decades of the Pittsburgh sample.

The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research.

Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.

Clinical significance of sleep-disordered breathing in Alzheimer's disease. Preliminary data.

In a study of 15 probable Alzheimer's patients and 12 healthy elderly control subjects, Alzheimer's patients had a significantly higher apnea index (patients versus controls, mean +/- SD: 6.3 +/- 6.6 vs 1.8 +/- 2.7, P less than .05) and greater maximal duration of apnea (patients versus controls, median: 50.0 vs 28.5 seconds, P less than .001), but no significant increase in oxyhemoglobin desaturation compared with controls. (The accepted normal threshold for abnormality is an apnea index more than 5.) Although three of seven psychometric tests (odd-even, category retrieval, face-hand test) showed diurnal effects on one or more of their subscores, with Alzheimer's patients having significantly poorer scores at the AM than at PM testing, overnight change scores in the psychometric tests were not significantly correlated with severity of sleep-disordered breathing. Further, only 18.1% of the disruptive (ie, requiring intervention) nocturnal behaviors of the Alzheimer's patients were temporally linked to sleep-disordered breathing. The current data suggest that sleep-disordered breathing in nonmedicated Alzheimer's patients is relatively mild and is not a predictor of either overnight mental status changes, of disruptive nocturnal behaviors, or of daytime behavioral fluctuations. Additional studies of more severely demented patients and possibly of sleeping pill effects would be useful in further evaluating the role of sleep apnea in Alzheimer behavioral changes.

Predicting mortality in mixed depression and dementia using EEG sleep variables.

The authors report a study of electroencephalographic (EEG) sleep predictors of two-year mortality in 26 elderly patients with mixed symptoms of depression and cognitive impairment. Patients who had died by two-year follow-up were characterized by significantly longer rapid eye movement (REM) sleep latencies at baseline, less robust REM sleep rebound following all-night sleep deprivation, and baseline apnea-hypopnea indexes greater than 3. Logistic regression analysis using the apnea-hypopnea index value and REM latency correctly predicted 77% of survivors and non-survivors. Survival time following initial measurements was significantly correlated with REM sleep time (r = 0.78, p less than .02) and duration of first REM sleep period (r = 0.75, p less than .02). The authors speculate that changes in these predictor variables may indicate impairment in the cholinergic control of cognitive function, REM sleep, and respiratory function.

Stability of EEG sleep and sleep quality in healthy seniors.

When the electroencephalogram-recorded (EEG) sleep of 19 healthy seniors (9 men, 10 women) aged 60-82 years was restudied after an average interval of 2.2 years, most measures of EEG sleep and sleep quality were stable over time. Both elderly men and women showed more awakenings during the second recording series, but no change in visual or computer-scored delta activity. Furthermore, gender-dependent sleep changes were noted only in phasic rapid eye movement (REM) measures (increasing in men, decreasing in women). Reports of sleep quality were also stable over time despite the increase in awakenings, with women reporting a lower sleep quality than men.

Diagnostic performance of nocturnal penile tumescence studies in healthy, dysfunctional (impotent), and depressed men.

Nocturnal penile tumescence (NPT) studies were evaluated in 17 men with a clinical diagnosis of organic erectile dysfunction in comparison to age-matched healthy controls (n = 17) and depressed men (n = 17). The dysfunctional group had significantly fewer NPT episodes and reduced maximal penile tip changes when compared to healthy controls and depressed patients. Further, the dysfunctional group had significantly diminished erectile fullness and reduced penile rigidity. Diagnostic performance of polygraphic (night 1) and visual inspection (nights 2 or 3) components of the NPT protocol were examined in these criterion groups. A diagnostic classification based on polygraphic measures successfully discriminated 73.5% of dysfunctional and healthy control subjects, but classified 47% of depressives in the dysfunctional range. Use of visual inspection indices correctly identified 88% of the dysfunctional sample and 94% of normal controls, and reduced the "false-positive" rate in depression to only 18%. Results support the diagnostic utility of NPT studies, particularly when enhanced by visual inspection procedures. Nevertheless, the presence of major depression may confound interpretation of such studies.

Electroencephalographic sleep in depressive pseudodementia.

Twenty-six patients with mixed symptoms of depression and cognitive impairment were studied with serial clinical ratings and sleep electroencephalograms during a one-night sleep-deprivation procedure. A subgroup of these patients with depressive pseudodementia (n = 8) had less severe symptoms of dementia at baseline and showed significant improvements in both Hamilton Depression Rating Scale scores and Profile of Mood States tension scores following sleep deprivation, while another subgroup of patients having primary degenerative dementia with depression (n = 18) showed no change or worsening in Hamilton depression and Profile of Mood States tension ratings. Baseline sleep measures demonstrated significantly higher rapid eye movement (REM) percent and phasic REM activity/intensity in pseudodemented compared with demented patients. While both groups had increases in sleep efficiency, sleep maintenance, and slow-wave sleep following sleep deprivation, recovery night 2 was characterized by greater first REM period duration in depressive pseudodementia than in dementia. These differences in REM sleep rebound (using an REM period 1 cutoff of greater than or equal to 25 minutes) permitted correct identification of 88.5% of patients. Implications of these data for current theories regarding sleep, aging, and psychopathology are discussed.

Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data.

Using electroencephalographic sleep data from a sample of 235 elderly subjects, discriminant function analyses of sleep alterations in depression and dementia were performed. Overall, 80% of patients were correctly classified using a backward discriminant function analysis, and 81% with a general stepwise discriminant function analysis. Four measures contributed to the separation of depressed and demented patients: rapid eye movement (REM) sleep latency (lower in depressives); REM sleep percent (higher in depressives); indeterminate non-REM sleep percent (higher in demented patients, reflecting greater loss of spindles and K complexes); and early morning awakening (more marked in depressives). When both discriminant functions were subjected to cross-validation in independent subsamples, both procedures correctly identified 78% of patients. The classification functions derived from nondemented depressed and nondepressed demented patients were applied to a mixed-symptom group (n = 42). Overall, 27 patients (64%) with either depressive pseudodementia or dementia with depressive features were correctly classified using the same four predictor variables. These findings suggest that sleep physiological alterations of depression and dementia reflect between-group differences in sleep continuity, sleep architecture, and REM sleep temporal distribution, and that the differences are statistically reliable, in both diagnostically pure and mixed clinical presentations. These findings are discussed in the context of current hypotheses of sleep regulation and its mechanisms.

Sleep deprivation as a probe in the elderly.

Decreased slow-wave sleep (SWS) and sleep continuity are major effects of healthy aging and of associated psychopathological states. Using sleep deprivation, we studied the extent to which age- and psychopathology-related sleep "decay" is reversible in aged normal, depressed, and demented subjects. Depression or probable Alzheimer's dementia compromised the augmentation of sleep continuity and SWS seen in healthy elderly following sleep deprivation. Rapid eye movement (REM) latency decreased during recovery sleep in the controls but increased in both patient groups. Compared with demented patients, depressed elderly had greater severity of sleep continuity disturbance both before and after sleep deprivation, a more protracted course of recovery sleep, and increased slow-wave density in the second non-REM (NREM) sleep period (during recovery). The REM sleep time was diminished in dementia compared with depression both at baseline and during recovery sleep. These differential effects of age, health, and neuropsychiatric disease on recovery from sleep loss are relevant to recovery or reversal theories of sleep and have implications for daytime well-being in the elderly.

Sleep deprivation effects in older endogenous depressed patients.

In a drug-free group of 15 older endogenous depressed inpatients, all-night sleep deprivation (SD) was associated with a significant decrease in Hamilton depression scores and in Profile of Mood States self-ratings of depression. Six of 15 patients (40%) were responders to SD, as evidenced by greater than or equal to 30% improvement in Hamilton ratings. While symptomatic improvement was short-lived (8 of 15 patients worsened after 1 night of recovery sleep), five patients showed further improvement after 1 night of recovery sleep. The final two patients had an increase in Hamilton ratings after sleep deprivation, with a return to baseline values after 1 night of recovery sleep. Responders (but not nonresponders) showed significant improvement in sleep latency, sleep efficiency, and slow wave sleep during recovery sleep (as did controls). The SD Hamilton depression rating (at 9 a.m. after all-night sleep deprivation) showed a significant inverse correlation with the increase in slow wave sleep (SWS) minutes and in SWS % from baseline to first recovery night. Responders also had significantly larger increases in SWS minutes than did nonresponders (53.8 vs. 7 minutes). Similarly, the % change in Hamilton depression ratings was predicted by baseline Stage 4 sleep. These findings suggest that there is a mutual interaction between the process of sleep regulation and the symptoms of depression. They also confirm a prediction from the two-process model of sleep regulation--namely, that improved sleep initiation and maintenance and increased SWS, attained by SD, are associated with clinical improvement.