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.

REM sleep enhancement by bupropion in depressed men.

OBJECTIVE: The authors compared the effects of bupropion, fluoxetine, and cognitive behavior therapy on EEG sleep in depressed subjects. METHOD: All-night sleep EEG studies were performed before treatment and after partial or full remission on 18 men with depression diagnosed according to Research Diagnostic Criteria and randomly assigned to treatment with either bupropion (N = 7) or fluoxetine (N = 11). Response to these drugs was measured by changes in Hamilton Depression Rating Scale scores. Pre- and posttreatment EEG sleep study results before and after treatment with cognitive behavior therapy were also available for 18 men matched in age and severity of Hamilton depression scale score, and one-time EEG sleep measures were available for 36 men who were not depressed. RESULTS: REM latency was reduced and REM sleep percent and REM time increased after treatment in the depressed men given bupropion. These effects contrasted with the effects of fluoxetine and cognitive behavior therapy. CONCLUSIONS: This study represents the first report of an antidepressant medication that shortens REM latency and increases REM sleep. If confirmed, this finding may require a revision of our current understanding of the relation among depression, REM sleep, and anti-depressant mechanisms.

Polysomnographic studies of unmedicated depressed men before and after cognitive behavioral therapy.

OBJECTIVE: Differentiation of stable, trait-like characteristics from more episodic or state-dependent disturbances will be helpful in gaining a better understanding of the pathophysiology of depression. However, research in this area has been complicated by artifactual and clinical problems associated with pharmacologic treatment. In this investigation the authors used EEG sleep studies to assess medication-free depressed male patients before and after cognitive behavioral therapy. METHOD: Forty-five male patients with the diagnosis of major depression according to the DSM-III-R criteria and the Research Diagnostic Criteria underwent EEG sleep studies before and after 16 weeks of cognitive behavioral therapy, during which they were free of medication. In addition to the documentation of changes within these patients, the findings were compared with those for 47 healthy subjects, including 15 who were restudied 12-24 months after their baseline assessments. RESULTS: The EEG sleep profiles of the depressed patients showed a significant reduction in REM sleep density after treatment, suggesting "normalization" of an abnormal state-dependent process. By contrast, slow wave sleep and tonic REM measures, including reduced REM latency, were unchanged after treatment. CONCLUSIONS: These findings suggest that early in remission there is disaggregation of irreversible, trait-like correlates of depression (e.g., diminished slow wave sleep and reduced REM latency) from more reversible disturbances (e.g., increased REM density).

Do depressed men and women respond similarly to cognitive behavior therapy?

OBJECTIVE: A great majority of the evidence pertaining to the effectiveness of the time-limited psychotherapies as treatments of major depression are derived from studies of either predominantly or entirely female subject groups. Depressed men and women differ in a number of important respects that may alter the course of affective disorder, and as a result, they may also differ in their responses to psychotherapy. In this study the outcomes of 40 men and 44 women treated with cognitive behavior therapy were compared. METHOD: The patients were interviewed with the Schedule for Affective Disorders and Schizophrenia and diagnosed according to the Research Diagnostic Criteria and DSM-III-R criteria. Subsequently, they were assessed every other week (with the Hamilton Depression Rating Scale, Beck Depression Inventory, and Global Assessment Scale) during a standardized, time-limited cognitive behavior therapy protocol. The outcomes of the men and women were compared by means of a series of analyses of variance and covariance and survival analyses. RESULTS: There were several significant pretreatment differences, and the men attended significantly fewer therapy sessions than the women. Although the men and women generally had comparable responses, patients with higher pretreatment levels of depressive symptoms, particularly women, had poorer outcomes. CONCLUSIONS: This study provides further evidence of gender-specific differences in depressed patients' symptoms and treatment utilization. Cognitive behavior therapy appears to be a comparably useful outpatient treatment for men and women. However, either more intensive cognitive behavior therapy or alternative methods of treatment may be warranted for patients with more severe syndromes.

Affect intensity and phasic REM sleep in depressed men before and after treatment with cognitive-behavioral therapy.

This article explored the relationship between daytime affect and REM sleep in 45 depressed men before and after treatment with cognitive-behavioral therapy and in a control group of 43 healthy subjects. The intensity of daytime affect (as measured by the sum of positive and negative affects) in depressed men correlated significantly and positively with phasic REM sleep measures at both pre- and posttreatment. This relationship was not found in healthy control subjects. In depressed men, both affect intensity and phasic REM sleep measures decreased over the course of treatment. The results suggest a relationship between phasic REM sleep and intensity of affect reported by depressed men. On the basis of this preliminary observation, it was hypothesized that abnormalities in phasic REM sleep in depressed patients are related, in part, to fundamental alterations in the intensity of their affective experience.

Metabolic and physiologic consequences of nortriptyline treatment in the elderly.

The challenge in the pharmacotherapy of affective disorders is shifting to maintenance treatment. Hence, there is a need for systematic data on the somatic effects of long-term medication use. Twenty-six depressed patients (age > 60 yr) treated with therapeutic concentrations of nortriptyline were evaluated after an average of 7 months for changes in lipoproteins and cardiovascular parameters. Twelve patients were tested for debrisoquine (P450 2D6) metabolic status and creatinine clearance at these same intervals. There was no significant change in cholesterol levels, but triglycerides and very-low-density lipoproteins (VLDL) were significantly increased. Heart rate was also elevated by a mean of 15 beats per minute, and there were modest but significant increases in cardiac conduction parameters. Creatinine clearance declined significantly (by 34%), and blood pressure was unchanged. Small decrements in P450 2D6 could be quantitated. Older patients treated with maintenance psychotropic medications should be evaluated at the regular intervals, particularly with regard to the age-related complications of multiple illness and medications.

Correlation of nocturnal penile tumescence and daytime affect intensity in depressed men.

Although depressed patients have been shown to have diminished nocturnal penile tumescence (NPT), there remains considerable variability of NPT in depression. We hypothesized that affective experience during the day accounts for some of this variability. Forty-five depressed men had assessments of affect intensity and affect balance, NPT, and daytime sexual function, both before and after treatment with Beck's cognitive behavior therapy (CBT). Forty-three normal control subjects were studied for comparison. Daytime affect intensity in depressed men, but not in control subjects, correlated significantly and positively with measures of NPT duration and rigidity both before and after treatment, regardless of the adequacy of daytime sexual function. When the effect of daytime affect on REM activity was controlled, the observed correlations became nonsignificant at pretreatment, but remained significant at posttreatment. Neuropharmacologically mediated changes in arousal responsivity associated with depression may underlie the observed relation between daytime affect intensity, rapid eye movement activity, and NPT.

Are buckling force measurements reliable in nocturnal penile tumescence studies?

The study of nocturnal penile tumescence (NPT) is frequently used to evaluate male erectile dysfunction. Buckling force, a measure of rigidity, is an important part of this evaluation, but its reliability is unknown. Accordingly, we studied the reliability of buckling force measurement and the stability of "maximum buckling force" between consecutive NPT series repeated in the same subject. For individual subjects, we correlated buckling forces for separate episodes of sleep-related tumescence that were of comparable fullness (0-100%) as rated by a technician's visual estimates. For healthy control subjects, test-retest correlations were > 0.8 both within-night and across study series separated by an average of 70 weeks. In depressed men, correlations within nights were > 0.9, but fell to 0.64 across study series separated by an average of 21 weeks. Despite the high reliability of buckling force measurement, we found little stability of "maximum buckling force" between NPT series for individual subjects. Considerable variability in the maximum degree of penile rigidity was seen over time despite a constant level of reported daytime erectile function. We conclude that although penile rigidity is one of the more important variables in the assessment of male erectile dysfunction and can be measured reliably, the instability of maximum rigidity during sleep-related erections suggests that it is, at best, an imprecise correlate of daytime erectile function.

Sexual function in depressed men. Assessment by self-report, behavioral, and nocturnal penile tumescence measures before and after treatment with cognitive behavior therapy.

Clinicians have long associated depression with alterations in sexual function, predominantly loss of sexual interest. In a longitudinal study measuring self-report, behavioral, and nocturnal penile tumescence variables before and after treatment with cognitive behavior therapy in an unmedicated sample of 40 outpatient depressed men, we found, contrary to expectation, that sexual activity per se was not reduced during the depressed state. Rather, loss of sexual interest appeared to be related to the cognitive set of depression, ie, loss of sexual satisfaction that then improved with remission from depression. Depressed men were heterogeneous, however, with respect to sexual behavior, eg, an anxious and more chronically depressed subgroup of men who did not have remissions with cognitive behavior therapy reported increased sexual interest and sexual activity. Also, contrary to expectation, nocturnal penile tumescence abnormalities in depressed men did not reverse when measured in early remission, nor did nocturnal penile tumescence measures correlate significantly with behavioral measures of sexual function. Nocturnal penile tumescence alterations in depression may thus be similar to other persistent electroencephalographic sleep abnormalities seen in depressed patients in remission, in being more trait-like than statelike.

Napping and 24-hour sleep/wake patterns in healthy elderly and young adults.

OBJECTIVE: To examine differences between healthy elderly and young adults in daytime napping, nocturnal sleep, and 24-hour sleep/wake patterns. A second objective was to determine whether elderly subjects with more and less frequent naps differed in their clinical features or nocturnal sleep. DESIGN: Survey by sleep/wake logs and polysomnography. Comparison by age. SETTING: Sleep/wake logs were completed in the subjects' homes. Polysomnographic studies were conducted on an outpatient basis in a sleep and chronobiology research laboratory. SUBJECTS: Convenience samples of forty-five healthy subjects over 78 years of age (21M, 24F) and 33 healthy adults between 20 and 30 years of age (20M, 13F). MAIN OUTCOME MEASURES: Using self-reports, we estimated the frequency and timing of daytime naps; timing, duration, and quality of nocturnal sleep; and 24-hour patterns of sleep and wakefulness. Also polysomnographic sleep measures. RESULTS: Compared to young adults, elderly subjects reported a greater mean number of daytime naps (P = .004), shorter nocturnal sleep with more wakefulness and earlier sleep hours (P less than .003 for each), and a trend for a shorter 24-hour sleep fraction. Among the elderly, more-frequent and less-frequent nappers did not differ in clinical ratings, self-report sleep measures, or polysomnographic measures. There was a trend for more sleep-disordered breathing and periodic limb movements in more frequent nappers. CONCLUSIONS: These findings are consistent with an age-related decrease in amplitude of the circadian sleep propensity rhythm, or with the expression of a semi-circadian (12-hour) sleepiness rhythm. However, we cannot exclude the additional possibility that napping results from lifestyle factors and nocturnal sleep pathologies in a subset of the elderly.

Shifts in affective balance during cognitive therapy of major depression.

Thirty-two outpatient depressives were treated by experienced therapists during a 16- to 20-week, 20- to 24-session cognitive-behavioral therapy (CBT) protocol. Patients were classified as CBT responders (n = 22) or nonresponders (n = 10) on the basis of independent clinical ratings of Hamilton (1960) depression severity. Point and confidence interval estimation procedures yielded results consistent with hypotheses derived from the states-of-mind (SOM; Schwartz & Garamoni, 1986) model. At posttreatment, CBT responders shifted the balance of positivity and negativity to the optimal range, whereas nonresponders remained in a predominantly negative SOM. Response status was related more strongly to change in positivity than in negativity. Findings support the view that clinical response to CBT depends on reducing negativity and increasing positivity until an optimal balance is achieved.

Debrisoquine hydroxylation phenotyping in geriatric psychopharmacology.

The metabolic ratios (MRs) between debrisoquine (DBQ) and 4-hydroxydebrisoquine in urine after a single dose of 10 mg DBQ was determined in 175 unmedicated, healthy subjects older than age 59 (mean of 75 years). Creatinine clearance was determined on the same 8-hour urine collection. Test procedures were well tolerated in all cases. Although age was significantly correlated with creatinine clearance (r = -.38), there was no relationship between age and MR. Analysis by kernel density estimation revealed a bimodal distribution of MRs with an antimode of 11.6. Six subjects (3.4%) were categorically slow DBQ metabolizers (MR greater than 11.6). The proportion of elderly slow metabolizers approaches the lower range determined in a younger population. Our findings, that DBQ oxidative metabolism does not necessarily change with aging, alone, and that (genetic) slow DBQ metabolizers endure into old age, remaining at risk for treatment with many commonly used psychotropics, suggests the need to study the relevance of metabolic phenotyping in elderly psychiatric patients.

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.