Ann B. McEachran

Comparison of full-dose versus half-dose pharmacotherapy in the maintenance treatment of recurrent depression

Recent evidence points to the prophylactic efficacy of maintaining recurrent unipolar patients on the same dose of antidepressant medication that was used to treat the acute episode (Frank et al., 1990; Kupfer et al., 1992). Therefore, the question of whether such patients should be tapered to a lower maintenance dose after successful resolution of an acute episode is clearly important. In this report we describe a small randomized clinical trial in which patients were assigned to either full-dose or half-dose maintenance treatment for a period of 3 years. Survival analysis suggests that superior prophylaxis can be achieved with a full-dose as compared to a half-dose maintenance treatment strategy (p < 0.07). Mean survival time for the full-dose subjects was 135.17 (SE 19.75) weeks as compared to 74.94 (SE 19.78) weeks (median of 43.1 weeks) for the half-dose subjects. We conclude that for patients who have suffered several recurrences, full-dose maintenance treatment is the more effective prophylactic strategy.

Comparison of effects of desipramine and amitriptyline on EEG sleep of depressed patients

Despite their widespread use, there are few data concerning the effects of tricyclic antidepressants on EEG sleep in depression. The present study documented the effects of desipramine (DMI, n=17) and amitriptyline (AT, n=16) upon EEG sleep in hospitalized depressed patients as part of a double-blind protocol involving 28 days of active treatment. Compared to placebo, patients receiving DMI showed somewhat worsened sleep continuity, particularly after 1 week of administration when the dose was 150 mg/day. On the other hand, sleep architecture and REM measures showed a rapid suppression of REM sleep, and then partial tolerance for this effect was observed with continued administration of DMI for 3 weeks. DMI was a more potent suppressor of REM sleep, while AT was more sedative. Based on these differences in effects upon EEG sleep, a discriminant function was derived and resulted in a correct classification of 87.5% of AT cases and 76.5% of DMI cases. These results are discussed in terms of the differences in pharmacological profiels for uptake blockade and anticholinergic potency for these two compounds.

The Use of the Hamilton Rating Scale for Depression in Elderly Patients With Cognitive Impairment and Physical Illness

The authors performed a prospective study to assess the impact of cognitive impairment and medical burden on the Hamilton Ratingh Scale for Depression (Ham-D) scores in older psychiatric inpatients. Over 1 year, all patients admitted to an acute-care geriatric psychiatry unit were assessed with an instrument that includes an anchored version of the 17-uten Ham-D. Ham-D scores of 72 patients who met DSM-III-R criteria for a major depressive episode were compared with the scores of 31 patients who did not. The scores of a depressed and nondepressed patients were significantly different on admission but not at discharge. By contrast, the Ham-D scores of 11 depressed patients with a primary dementia did not differ either on admission or at discharge from the scores of 61 depressed patients without dementia. Controlling for psychiatric diagnosis, cognitive impairment had no significant effect on Ham-D scores. Medical burden accounted for less than 6% of the variance in admission Ham-D yields valid ratings of the severity of depressive symptoms in elderly patients with a broad range of cognitive impairment and physical illness.

Electroencephalographic sleep profiles in single-episode and recurrent unipolar forms of major depression: I. Comparison during acute depressive states

The current study was conducted to examine if recurrent depression is associated with more severe disturbances of all-night EEG sleep profiles than single-episode depressions. Unmedicated sex- and age-matched groups of 22 single-episode (SE) and 44 recurrent unipolar (RU) outpatients with DSM-III-R/SADS/RDC major depression underwent 2 consecutive nights of EEG sleep recording. Multivariate analyses of covariance (MANCOVAs) and/or analyses of covariance (ANCOVAs) were performed on six sets of sleep measures. Recurrent unipolar depression was associated with significantly increased phasic REM sleep, as well as increased REM counts on the second night of study. Recurrent depression also was associated with significantly poorer sleep efficiency, although the groups did not show consistent differences in sleep architecture or slow-wave sleep. Our findings generally support the hypothesis that recurrent depression is associated with a more severe neurophysiologic substrate than phenotypically similar SE cases. Results are, for the most part, compatible with Posts (1992) model of illness progression, particularly with respect to greater disturbances of state-dependent sleep abnormalities in the RU cases. Longitudinal studies are needed to confirm the evolution of such changes prospectively.

Persistent effects of antidepressants: EEG sleep studies in depressed patients during maintenance treatment

Electroencephalographic (EEG) sleep studies represent a research tool that can be used to examine depressed patients over different phases of their illness. We examined the long-term effects of imipramine on EEG sleep in 27 subjects who completed 3 years of maintenance treatment on imipramine without experiencing a recurrence. The analyses were performed on EEG sleep data collected prior to acute treatment, after 3 months in maintenance, and every 3 months thereafter. The major aim was to examine specific changes in rapid eye movement (REM) and slow-wave sleep (SWS) as they unfolded over the course of illness and recovery during long-term drug maintenance. The acute changes in the sleep profile produced by antidepressants remained essentially the same throughout the entire period of drug administration. The REM sleep parameters, which were affected immediately, remained essentially unchanged thereafter, even as long as 3 years into maintenance treatment. A rapid redistribution of slow-wave sleep in the first part of the night was also observed without an increase in the total amount of slow-wave sleep throughout the night. The application of spectral analysis confirmed that the sleep changes following drug administration remained stable throughout all phases of drug treatment. Thus, it appears that sustained clinical improvement is accompanied by persistent sleep alterations on tricyclic antidepressant medication.

Aspects of short REM latency in affective states: A revisit

Electroencephalographic (EEG) sleep changes in affective disorders have been characterized by sleep continuity, slow wave sleep, and rapid eye movement (REM) abnormalities. The most commonly cited feature, however, has been shortened REM latency. Because the diagnostic and prognostic significance of shortened REM latency has been debated, this issue was reexamined in a group of 186 psychotic and nonpsychotic depressed inpatients and outpatients. The analyses suggest an increased frequency of sleep onset REM periods in psychotic depression and in elderly depressed patients (psychotic or nonpsychotic).

Differential effects of amitriptyline and of zimelidine on the sleep electroencephalogram of depressed patients

The effects of amitriptyline (n = 14) or zimelidine (n = 13) on the sleep electroencephalogram of hospitalized depressed patients were assessed in a double‐blind protocol involving 28 days of active dosing. Zimelidine induced no immediate improvement in sleep continuity, and even after 3 wk on zimelidine subjects tended to have longer sleep latency, more awakenings, and lighter non‐rapid eye movement (REM) sleep than before taking the drug. Zimelidine did, however, induce a rapid and persistent alteration of sleep architecture and selected REM measures. REM sleep, which was suppressed over the first two nights on zimelidine, was maximally suppressed after 1 wk, but by 3 wk there was some tolerance for selected REM measures. While zimelidine induced none of the sedative effects of amitriptyline, both were equivalent in their REM‐suppressant effects. These findings are discussed in terms of the differences in uptake blockade and anticholinergic potency in these two drugs.

EEG sleep profiles and recurrent depression

Earlier investigations have suggested that electroencephalographic (EEG) sleep may be altered as a function of the duration of an episode of depression. We compared the EEG sleep profiles in a group of recurrent depressives who had been depressed for less than 6 weeks with their sleep profiles as measured during their previous episode of depression. Findings in this sample of 32 patients point to the presence of specific rapid eye movement (REM) sleep abnormalities as being more pronounced earlier in the course of a depressive episode. Changes in REM latency and REM activity were also reflected in reductions in EEG spectral power in almost all bandwidths during the first REM period of the recurrent episode. These results are not easily explainable on the basis of traditional measures of clinical severity or the number of episodes.

Electroencephalographic sleep studies in depressed patients during long-term recovery

Analytic electroencephalographic (EEG) sleep procedures were used to examine specific changes in rapid eye movement (REM) and slow wave sleep (SWS) as they unfolded during depressive illness and recovery. The subjects were 15 patients with recurrent depression who remained well during 3 years of nonpharmacologic maintenance treatment without a recurrent episode of major depression. The analyses were performed on EEG sleep studies conducted before acute treatment, after 3 months in maintenance treatment, and every 3 months thereafter for 3 full years of maintenance treatment. There was no change between the index sleep and sleep during the first year of maintenance treatment as determined by period analysis or visual inspection of REM sleep parameters, except that average REM counts decreased over time. Thus, it is possible that REM parameters may represent one indicator of long-term recovery from depression. Finally, a significantly higher amount of 12-20 Hz spectral power density was found during the index episode than during the period of remission.

Imipramine and sexual dysfunction during the long-term treatment of recurrent depression.

Ninety patients in the maintenance therapy phase of the Pittsburgh Study of Maintenance Therapies in Recurrent Depression (Frank et al., 1990) were studied to determine possible relationships between the type of therapy (imipramine versus no drug) and the level of sexual functioning. The level of sexual functioning was determined by a composite subscale score of the Social Adjustment Scale which assessed (1) current level of enjoyment and interest in sex; (2) change in interest; (3) current frequency of sexual intercourse; (4) change in frequency; and (5) pain and/or difficulty reaching orgasm. Loss of libido was assessed by both the Hamilton Rating Scale for Depression and the SCL-90. Logistic regression analysis revealed no relationship between treatment with active imipramine and sexual functioning for the total group, or for females alone. Analysis of males alone revealed a decreased interest in sex among those treated with imipramine, but no significant differences in frequency or problems. The implications for maintenance pharmacotherapy and the cost/benefit ratio of unacceptable side effects versus drug efficacy are discussed.