Sexual sequelae of antihypertensive drugs: treatment effects on self-report and physiological measures in middle-aged male hypertensives.

Antihypertensive drugs are commonly associated with adverse side effects in both clinical and laboratory studies. We investigated the sexual sequelae of several major classes of antihypertensive drugs (e.g., beta blockers, central alpha agonists, diuretics) in normal males and in hypertensive patients. We compared the effects of four widely used agents (methyldopa, propranolol, atenolol, hydrochlorothiazide-triamterene) and placebo, in a selected sample of 21 sexually dysfunctional male hypertensives, 13 of whom completed all five phases of the study. Each study drug was administered for a 1-month treatment period, followed by a 2-week, single-blind washout phase, according to a randomized, Latin square crossover design. Dependent variables for the study included a broad range of hormonal, NPT, and self-report measures of sexual response. Results indicated a lack of consistent drug effects on measures of sexual response, although more frequent sexual and nonsexual side effects were observed with methyldopa and propranolol. As in our previous studies, age was negatively correlated with both hormonal and NPT measures, whereas changes in blood pressure were not significantly related to sexual function scores. Results do not support the hypothesis that sexually dysfunctional males are at greater risk for adverse sexual sequelae when treated with centrally active agents or diuretics.

Beta blocker effects on heart rate during sleep: a placebo-controlled polysomnographic study with normotensive males.

Although the effect of beta blockers on heart rate (HR) at rest, during exercise, and by ambulatory electrocardiography during the day and night has been studied extensively, data on the effect of these drugs on heart rate during the various stages of sleep are not available. We performed overnight polysomnography and exercise testing in a randomized, double-blind, placebo-controlled, Latin square crossover study of four beta blockers with different ancillary properties (atenolol 100 mg daily, metoprolol 100 mg, pindolol 10 mg, and propranolol 80 mg), on 30 healthy men aged 23-40 years (29.4 +/- 4.3) (mean +/- SD). At rest pindolol increased HR by 4.7 beats/min +/- 13.1 (p less than 0.05), while beta blockers without intrinsic sympathomimetic activity (ISA) decreased HR (p less than 0.0001) by 6.1 +/- 8.8 (atenolol), 5.8 +/- 8.4 (propranolol), and 5.0 +/- 9.4 (metoprolol). Exercise at 125 W increased HR on placebo by 76.4 +/- 18.4 beats. Compared to placebo all beta blockers were associated with lower (p less than 0.0001) exercise HR by 18.3 +/- 23.2 atenolol, 21.1 +/- 15.5 metoprolol, 16.8 +/- 14.1 pindolol, and 20.8 +/- 13.1 propranolol [not significant (NS) among beta blockers]. Thus the effect of beta blockers on heart rate was magnified during exercise. Mean and maximum HR were higher in rapid eye movement (REM) than in nonREM (NREM) sleep (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

CNS side effects of centrally-active antihypertensive agents: a prospective, placebo-controlled study of sleep, mood state, and cognitive and sexual function in hypertensive males.

A prospective, placebo-controlled, comparative evaluation was conducted on two widely prescribed, sympatholytic antihypertensive agents with known CNS effects. In order to separately assess these effects in younger and older male hypertensives, patients were assigned to either of two treatment studies based on age. For study I, 24 males aged 31-59 (mean = 49.8; SD = 7.4) with mild hypertension (mean DBP = 100.2 mm Hg; SD = 8.0) received 3 months of treatment with propranolol (20-80 mg bid), clonidine (0.1-0.3 mg bid), or double-blind placebo in a counterbalanced, crossover design. For study II, 23 elderly hypertensive males (mean DBP = 102.6 mm Hg; SD = 8.2) aged 60-78 years (mean = 65.1; SD = 4.6) were randomized to propranolol (20-40 mg bid) or double-blind placebo therapy. Patients received cognitive testing, mood assessments, and all-night polysomnographic evaluations before and after each treatment period. Multivariate analysis of EEG sleep data was statistically significant for study I, with significant univariate effects on four of the six primary sleep variables: total sleep time was reduced, sleep maintenance decreased, REM latency increased, and percent total REM time was reduced. A similar MANOVA analysis for the effects of treatment on the sleep of older patients (study II) was not significant. However, propranolol administration was found to be associated with a significant decline in cognitive performance in these patients. Significant mood effects were observed with each of the study drugs, and nocturnal penile tumescence (NPT) was significantly decreased in both younger and older patients. Overall, this research suggests that distinct patterns of CNS effects are associated with each of the antihypertensive agents studied.

Sleep apnea in Alzheimer's dementia: correlation with mental deterioration.

In a prospective study of sleep-disordered breathing among healthy elderly controls (N = 23), major depressives (N = 17), and demented patients with probable Alzheimer's disease (N = 21), sleep apnea (defined as an apnea index of 5 or more) was found in 42.9% of demented patients, 17.6% of depressives, and 4.3% of controls (chi 2 = 9.90, p less than .01). A significant association between sleep apnea and dementia of the Alzheimer type was found in women but not in men. Moreover, severity of dementia was significantly correlated with apnea index. Possible neuropathologic and clinical implications of these findings are discussed.

EEG sleep in elderly depressed, demented, and healthy subjects.

In a prospective study of EEG sleep patterns in 25 elderly depressives, 25 elderly demented patients, and 25 healthy, elderly control subjects, the sleep of depressives was characterized by reduced REM sleep latency, increased REM percent and first REM period density, and altered temporal distribution of REM sleep, as well as by diminished sleep maintenance (correlated significantly with Hamilton ratings of depression: multiple R = -0.42, p less than 0.05). In contrast, the sleep of demented patients showed reduced REM sleep percent, but normal REM temporal distribution, increased loss of spindles and K-complexes (the latter correlating significantly with severity of cognitive impairment as measured by the Folstein score: multiple R = -0.59, p less than 0.01), and less severe sleep maintenance difficulty than for depressives. An examination of REM latency demonstrated a skewed distribution in depression (i.e., 42% of nights with sleep-onset REM periods), but a normal distribution in the controls and demented subjects. A REM latency cut-off score of 30 min correctly classified 68% of all patients (kappa = 0.36; p less than 0.005), compared with 78% correctly identified in our retrospective study (Reynolds et al. 1983).

Slow wave sleep in elderly depressed, demented, and healthy subjects.

The application of automated analysis in the measurement of sleep electroencephalogram delta activity allows a more precise temporal description of slow wave sleep changes in normal and pathological aging than do standard, all-night, slow wave sleep measures. Thus, with a baseline crossing technique, elderly depressives were shown to have a higher delta count per minute during the second NREM sleep period than did controls or demented subjects. This difference reflected greater activity per minute in the 2-3 Hz frequency band (75-200 microV).

Depression in borderline patients: a prospective EEG sleep study.

The relationship between borderline personality disorder and primary major depression was studied prospectively using Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) interviews and electroencephalographic (EEG) sleep studies. Ten consecutively admitted borderline patients (a prospective sample), defined by Gunderson's Diagnostic Interview for Borderlines (DIB), underwent EEG sleep studies on two consecutive nights and were compared to previously reported samples of nonborderline depressed patients (defined by Research Diagnostic Criteria; RDC), normal controls, and DIB-defined borderline patients who had been referred "to rule out major depression" (a retrospective sample). EEG sleep data were analyzed visually and by automated techniques. Rapid eye movement (REM) latency values were similar in depressed and both borderline groups but significantly different from controls. Eighty-five percent of REM latency values in RDC major depressives were less than or equal to 65 minutes, compared to similar rates of 75% in the prospective sample of borderline patients and 65% in the retrospective sample, versus 35% for controls (chi 2 = 10.7, p less than 0.005). The REM latency in borderline patients did not vary with the severity of depression as measured by the Hamilton Rating Scale for Depression. In the prospective borderline sample, the major SADS-L diagnoses were chronic intermittent depression (five), current major depression (four) (two unipolar, two bipolar II), and labile personality (one). A convergence of nosologic and EEG sleep data is suggested, and supports the concept of a close relationship between criteria-defined borderline personality disorder and affective illness.

Sleep of healthy seniors: a revisit.

In an EEG sleep study of 40 healthy seniors (19 men and 21 women) aged 58-82 years, men could not maintain sleep as well as women and experienced less stage 3 sleep. The increased wakefulness after sleep onset among the men was particularly marked during the last 2 h of recording. REM density (during the first and second REM periods) showed an interaction of sex and age effects: thus, women in their 60s had higher REM density than men, whereas men in their 70s had higher REM density than women. In both men and women, however, regardless of age, the temporal distribution of REM sleep and REM density during the night was flat. Finally, only a mild degree of sleep-disordered breathing was noted, with positive age effects on apnea/hypopnea index and maximal duration of apnea. These findings are reviewed in relation to the sleep and aging literature.

Elevated red blood cell/plasma choline ratio in dementia of the Alzheimer type: clinical and polysomnographic correlates.

In a prospective study we have observed a shift in distribution of red blood cell (RBC)/plasma choline ratios among patients with probable dementia of the Alzheimer type (DAT), compared with healthy controls and depressed patients. Fifteen of 22 DAT patients (68%) showed RBC/plasma choline ratios greater than 1.9, in contrast to 9 of 26 healthy controls (35%) and 7 of 20 depressives (35%). These significant differences confirm and expand earlier observations. The subgroup of DAT patients with elevated RBC/plasma choline ratios is older and more cognitively impaired, shows later onset of dementia, and has less rapid eye movement (REM) sleep than the DAT subgroup with normal RBC/plasma choline ratios. Within the entire group of DAT patients, moreover, the RBC/plasma choline ratio shows a significant inverse correlation with REM sleep latency. These findings are discussed in relation to abnormalities in other nonneural Alzheimer tissues and within the context of cholinergic involvement in both DAT and the timing of REM sleep.

Depressive psychopathology in male sleep apneics.

Depression has been reported to be frequent in sleep apnea syndromes. In a sample of 25 consecutive male sleep apneics, 40% met Research Diagnostic Criteria for an affective disorder or for alcohol abuse. A multiple regression analysis indicated that 61% of the variance in depression ratings could be explained by four variables: age, REM activity, REM latency (square root), and presence or absence of antihypertensive medications (multiple R = 0.78). The use of these variables in a discriminant function analysis correctly predicted the membership of 68% of the sample in either a low or high depression group (kappa = 0.44; p less than .01). These findings are reviewed in relation to other research on age-related sleep changes and vulnerability to depression.

Persistent psychophysiologic insomnia: preliminary Research Diagnostic Criteria and EEG sleep data.

Some patients with persistent psychophysiologic insomnia have a history of generalized anxiety, minor depression, or drug misuse. Their sleep resembles sleep of patients with generalized anxiety (except for night 2 improvement in the insomniacs' sleep continuity) but differs from sleep of patients with major depression.

EEG sleep of normal healthy children. Part I: Findings using standard measurement methods.

Despite the increasing application of all-night electroencephalographic (EEG) sleep studies to children for clinical as well as for research purposes, readily available normal EEG sleep standards for the period of childhood have remained sparse and, at present, reflect data on only approximately 100 children 6 to 16 years of age. As part of a large scale study examining various aspects of EEG sleep among children, findings derived using standard recording and scoring methods are reported for a new sample of nearly 100 normal, healthy children and are compared with existing standards. Data obtained add substantially to the existing database and generally confirm findings of previous normative reports on children in this age range.

Multiple Sleep Latency Test findings in Kleine-Levin syndrome.

Multiple Sleep Latency Test (MSLT) findings in a case of Kleine-Levin syndrome are reported for the first time. MSLT data indicate sleepiness as severe as in narcolepsy or obstructive sleep apnea and the occurrence of four sleep onset rapid eye movement (REM) periods, with a greater REM propensity at 2:00 p.m. and 4:00 p.m. than at 10:00 a.m. and 12:00 noon. The replication of such findings might suggest that Kleine-Levin syndrome could be considered a form of periodic REM sleep disinhibition. Therefore, the traditional hypothesis of diencephalic dysfunction may require modification to include the role of more caudal brain stem structures specifically activated during REM sleep.

REM latency in depression: is there one best definition?

The concurrent validity of different definitions of REM latency has been tested by comparing the ability of each definition to discriminate between primary depressives (outpatients and inpatients) and normal controls. In outpatients the percentage of cases correctly identified ranged from 62.5% to 70.8%; in inpatients, from 64.6% to 70.8%. REM latency definitions with the least stringent sleep-onset criteria yielded the lowest specificity. In contrast, the range of sensitivities yielded by different definitions was narrower and not clearly affected by sleep-onset criterion or exclusion/inclusion of wakefulness between sleep onset and first REM period. Furthermore, different definitions of REM latency correlated equally well (p less than 0.01) with Hamilton depression ratings. The shorter REM latencies in both outpatients and inpatients were associated with a later time of NREM sleep onset than in controls, rather than with an earlier REM sleep-onset time.

Sleep in narcolepsy and depression. Does it all look alike?

Depression has been reported to be frequent in narcolepsy and has been considered to be variously a reaction to chronic sleepiness or an endogenous expression of the pathophysiology of narcolepsy. Supporting the latter possibility are reports of similarities between the nocturnal rapid eye movement (REM) sleep of narcoleptics and inpatients with endogenous depression. In a comparison of 25 consecutive narcoleptics and 25 age-matched outpatient primary depressives, significant group differences were found in nocturnal EEG sleep measures of sleep continuity, sleep architecture, and REM sleep. Twenty per cent of the narcoleptic sample met Research Diagnostic Criteria (RDC) for a past history of major or chronic intermittent depression, but 60 per cent did not meet RDC criteria for any present or past psychiatric disorder. These findings mandate a cautious reevaluation of the nature of depressive symptoms in narcolepsy and leave open the question of whether there are common neurobiological control mechanisms in narcolepsy and depression.