米氮平治疗抑郁症患者的早期睡眠多导图改变

目的 通过睡眠多导图(PSG)客观评价米氮平治疗早期抑郁症伴失眠患者睡眠结构的影响及改善睡眠的疗效.方法 入组25例抑郁症伴失眠患者,在进行基线量表评估和PSG监测后开始服药,米氮平起始剂量每天15 mg,3 d后增至每天30 mg,睡前1 h服用;7 d后再次进行量表评估和PSG监测;观察治疗后失眠、焦虑抑郁症状、PSG的变化.结果 25例抑郁症伴失眠患者在米氮平治疗7 d后分别进行量表评分,显示各量表减分值分别为Athens失眠量表(7.92±3.86,t=10.255,P=0.000)、汉密尔顿抑郁量表(9.80±4.41,t=12.132,P=0.000)、汉密尔顿焦虑量表(6.84±5.57,t=6.137,P=0.000);PSG结果显示治疗总睡眠时间(min)延长(402.46±80.75,t=-2.990,P=0.006)、睡眠觉醒时间(min)缩短(80.38±48.02,t=2.972,P=0.007)、睡眠效率明显提高(76.17%±10.65%,t=-2.750,P=0.011),深睡眠比例显著增加(19.66%±11.43%,t=3.236,P=0.004),而入睡潜伏期和睡眠中清醒次数、快速眼动睡眠潜伏期、比例及出现次数无差异.结论 单一使用米氮平治疗抑郁症伴失眠患者起效快,同时能增加总睡眠时间、缩短睡眠觉醒时间、提高睡眠效率、增加深睡眠比例等,达到有效改善失眠.     

Acute effects of mirtazapine on sleep continuity and sleep architecture in depressed patients: a pilot study.

BACKGROUND: Mirtazapine, a clinically effective antidepressant, acts by antagonizing central alpha2-adrenergic and 5-HT2/5-HT3 receptors. No data are available regarding mirtazapine's effects on sleep architecture in patients with major depressive disorder. METHODS: Six patients meeting criteria for major depressive disorder and scoring > or =4 on the three Hamilton Depression Rating Scale sleep items were studied. Polysomnographic evaluations were performed at baseline and after 1 (15 mg at bedtime) and 2 weeks (30 mg at bedtime) of open-label mirtazapine treatment. RESULTS: Mirtazapine significantly decreased sleep latency and significantly increased total sleep time and sleep efficiency from baseline levels during week 1, with similar results observed after week 2. Mirtazapine did not significantly alter rapid eye movement sleep parameters. Clinically, Hamilton Depression Rating Scale and sleep disturbance ratings improved after treatment. CONCLUSIONS: Mirtazapine significantly improves sleep continuity in major depressive disorder patients with poor sleep quality at weeks 1 and 2 of treatment, while preserving sleep architecture.     

碳酸锂合并米氮平或氟西汀治疗双相抑郁的对照研究

目的评价米氮平合并碳酸锂治疗双相抑郁的疗效和安全性。方法将126例双相抑郁患者分为两组,研究组61例,应用米氮平合并碳酸锂,对照组65例,应用氟西汀合并碳酸锂,治疗8周。分别于治疗后第2、4、6、8周末用汉密尔顿抑郁量表(HAMD)和不良反应量表(TESS)比较两组的疗效和安全性。结果治疗后第2、4、6、8周末两组HAMD总分比较,差异均有显著性(P<0.05),研究组疗效优于对照组(P<0.05),两组脱落率比较差异有显著性(P<0.05),两组治疗后各时期TESS总分比较差异均无显著性(P>0.05),但研究组在治疗早期的嗜睡、困倦发生率较高、失眠发生率较低、胃肠道反应较少、治疗末体重增加较多(P均<0.05)。结论米氮平合并碳酸锂治疗双相抑郁疗效肯定,不良反应较少,依从性好。     

Polysomnography in patients with post‐traumatic stress disorder

Aims: The purpose of the present study was to investigate sleep structure in post‐traumatic stress disorder (PTSD) patients with and without any psychiatric comorbidities. The relationship between sleep variables and measurements of clinical symptom severity were also investigated. Methods: Sleep patterns of 24 non‐medicated male PTSD patients and 16 age‐ and sex‐matched normal controls were investigated on polysomnography on two consecutive nights. Six PTSD‐only patients and 15 PTSD patients with major depressive disorder (MDD) were also compared to normal controls. Sleep variables were correlated with PTSD symptoms. Results: Compared to the normal controls, the PTSD patients with MDD had difficulty initiating sleep, poor sleep efficiency, decreased total sleep time, decreased slow wave sleep (SWS), and a reduced rapid eye movement (REM) sleep latency. The PTSD patients without any comorbid psychiatric disorders had moderately significant disturbances of sleep continuity, and decreased SWS, but no abnormalities of REM sleep. REM sleep latency was inversely proportional to the severity of startle response. SWS was found to be inversely correlated with the severity of psychogenic amnesia. Conclusions: PTSD patients have disturbance of sleep continuity, and SWS deficit, without the impact of comorbid depression on sleep. The relationship between SWS and the inability to recall an important aspect of trauma may indicate the role of sleep in the consolidation of traumatic memories. The relationship between the severity of the startle response and REM latency may suggest that REM sleep physiology shares common substrates with the symptoms of PTSD.     

Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder

The goal of the present work is to assess for the relationship between the timing of clinical improvement and the resolution of depressive symptoms in Major Depressive Disorder (MDD). 182 MDD outpatients (40.5+/-9.7 years; 53.8% female) who responded following an 8-week, 20 mg, open trial of fluoxetine were included in the analysis. The symptoms questionnaire (SQ) and Beck hopelessness scale (BHS) were also administered to 83 and 153 of these patients, respectively. Onset of clinical improvement was defined as a 30% decrease in 17-item Hamilton depression scale (HDRS-17) scores. Controlling for baseline symptom severity, we then assessed for the relationship between the timing of clinical improvement and depressive symptom at endpoint. Earlier clinical improvement in responders predicted lower HDRS-17, BHS, SQ-depression, SQ-anxiety, but not SQ-somatic symptom or SQ-anger/hostility scores at week 8. This was true regardless of whether improvement was defined as a continuous measure (30% decrease in symptom severity), as a dichotomous measure (clinical response occurring in the first two weeks of treatment). In conclusion, earlier clinical improvement with fluoxetine treatment is predictive of greater symptom resolution at endpoint. Further studies exploring the impact of various treatment modalities and placebo on the timing of clinical improvement and symptom resolution in MDD are warranted.     

Mirtazapine in the treatment of adolescents with major depression: an open-label, multicenter pilot study

This multicenter, open-label study with a duration of 85 days was performed to evaluate the antidepressant efficacy and safety of mirtazapine (dose range, 30-45 mg) in 12-18-year-old adolescents diagnosed with major depression. Twenty-four (24) patients (15 female patients and 9 male patients) meeting the DSM-IV criteria for major depression and the Hamilton Rating Scale for Depression (HAM-D-17) score of 18 at baseline were enrolled in the study. The primary outcome measures were HAM-D-17, Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) scales. Any changes in symptoms of anxiety were measured using the Hamilton Anxiety Rating Scale (HAM-A). The average age of the 23 subjects, who were eligible for analysis, was 16.3 years (standard deviation (SD) 6.11, median 17.3). The mean daily dose of mirtazapine was 32.9 mg. Mirtazapine showed a marked efficacy on all rating scales and was well tolerated. Mirtazapine had a beneficial effect on sleep. A rapid onset of sleep and pattern of action was seen. No dropouts due to adverse events were recorded. The most common treatment-emergent adverse events were tiredness, increased appetite, and dizziness. The results of this study suggest that mirtazapine may be an effective treatment for major depression in adolescents.     

Sleep is undisturbed in elderly, depressed individuals who have not sought health care

Sleep deficits are commonly found in geriatric depressed patients, particularly shortened rapid eye movements (REM) latency, disturbed sleep continuity, and decreased slow wave sleep (SWS). Here we report the sleep patterns of community volunteers responding to ads about memory loss and depression. The two groups, 24 geriatric-onset major depressive disorder (MDD) subjects with a minimal history of seeking treatment for depression and 24 gender- and age-matched control subjects, significantly differed from each other on only one measure of sleep--sleep latency; the MDD group showed a modest but significant shortening of latency to fall asleep. All other sleep/wake measures, including REM latency, temporal distribution of REM sleep across the night, SWS, and measures of nighttime wakefulness did not differ between groups. This lack of significant sleep disturbance suggests that the sleep deficits reported in many studies of major depression may be related to factors underlying treatment-seeking behaviors, physical health status, severity of the depression, or heterogeneity within the MDD population with some types seeking treatment and others not seeking it, rather than depressive state per se. The data indicate that community-dwelling healthy elderly individuals who have a diagnosed major depression but who have not actively sought health care do not necessarily manifest the sleep disturbances thought to be characteristic of major depressive illness.     

Non-REM sleep instability in patients with major depressive disorder: subjective improvement and improvement of non-REM sleep instability with treatment (Agomelatine)

OBJECTIVE: To assess the importance of non-rapid eye movement (NREM) sleep disturbance in major depressive disorder (MDD) patients using cyclic alternating pattern (CAP) analysis, and to determine the usefulness of CAP analysis in evaluating treatment effect. METHODS: Baseline sleep-staging data and CAP analysis of NREM sleep was compared in 15 MDD patients (Hamilton depression scale score>20) and normal controls. Longitudinal evaluation of sleep changes using similar analysis during a treatment trial was also performed. ANALYSIS: A single-blinded researcher scored and analyzed the sleep of MDD and age-matched normal controls at baseline and during a treatment trial using the international scoring system as well as CAP analysis. RESULTS: MDD patients had evidence of disturbed sleep with both analyses, but CAP analysis revealed more important changes in NREM sleep of MDD patients at baseline than did conventional sleep staging. There was a significant decrease in CAP rate, time, and cycle and disturbances of phase A subtype of CAP. NREM abnormalities, observed by CAP analysis, during the treatment trial paralleled subjective responses. Analysis of subtype A phase of CAP demonstrated better sleep improvement. CONCLUSION: CAP analysis demonstrated the presence of more important NREM sleep disturbances in MDD patients than did conventional sleep staging, suggesting the involvement of slow wave sleep (SWS) in the sleep impairment of MDD patients. Improvement of NREM sleep paralleled subjective mood improvement and preceded REM sleep improvement. CAP analysis allowed objective investigation of the effect of treatment on sleep disturbances.     

High frequency EEG activity during sleep: characteristics in schizophrenia and depression.

Previous studies indicate that high frequency power (>20Hz) in the electroencephalogram (EEG) are associated with feature binding and attention. It has been hypothesized that hallucinations and perceptual abnormalities might be linked to irregularities in fast frequency activity. This study examines the power and distribution of high frequency activity (HFA) during sleep in healthy control subjects and unmedicated patients with schizophrenia and depression. This is a post-hoc analysis of an archival database collected under identical conditions. Groups were compared using multivariate analyses of covariance (MANCOVA) using group frequency by stage analysis. A multiple regression analyzed the association between HFA power and clinical symptoms. Schizophrenic (SZ) and major depressive disorder (MDD) patients showed significantly greater high frequency (HF) power than healthy controls (HC) in all sleep stages (p<0.0001). SZs also exhibited significantly greater HF power than MDD patients in all sleep stages except wakefulness (W) (p<0.05). In all groups, gamma (35-45Hz) power was greater in W, decreased during slow wave sleep (SWS) and decreased further during rapid eye movement (REM). Beta 2 (20-35 Hz) power was greater in W and REM than in SWS. Only positive symptoms exhibited an association with HF power. Elevated HFA during sleep in unmedicated patients with SZ and MDD is associated with positive symptoms of illness. It is not clear how HFA would change in relation to clinical improvement, and further study is needed to clarify the association of HFA to the state/trait characteristics of SZ and MDD.     

Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients

BACKGROUND: The necessity of antidepressant continuation-phase therapy following acute-phase response has resulted in the need to characterize the longer-term efficacy and safety of all new medications. Previous studies using "extension" protocols suggest that mirtazapine has sustained antidepressant effects. The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy, using a more rigorous, randomized, placebo-controlled discontinuation design. METHOD: An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine (flexibly titrated, 15-45 mg/day). Thereafter, 156 fully remitted patients (according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores) were randomly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo. RESULTS: Mirtazapine therapy reduced the rate of depressive relapse by more than half, with 43.8% of patients relapsing on treatment with placebo as compared with 19.7% of the mirtazapine-treated patients. The discontinuation rate due to adverse events was 11.8% for active mirtazapine therapy versus 2.5% for placebo. Although weight gain was significantly greater in the group receiving active medication during the double-blind phase (p = .001), patients taking mirtazapine gained only 1.4 kg (3.1 lb) across the 40 weeks of continuation therapy, and there was no difference in the rates of weight gain as a newonset adverse event. CONCLUSION: Continuation-phase therapy with mirtazapine is effective and well tolerated.     

Adjunctive atomoxetine for residual fatigue in major depressive disorder

OBJECTIVE: To assess the effectiveness and safety of atomoxetine as an adjunctive medication for residual fatigue in a naturalistic treatment setting. METHODS: A retrospective chart review was conducted to identify major depressive disorder (MDD) patients who had experienced significant symptom improvement (either partial response or remission) following treatment with conventional antidepressants but who were continuing to complain of fatigue. Fourteen such patients (42.2+/-13.4 years of age, five women, baseline HDRS 6.2+/-2.4) with a 17-item Hamilton Depression Rating Scale (HDRS17)<11 who received adjunctive atomoxetine for fatigue were included in the report. Antidepressants augmented were the selective serotonin reuptake inhibitors (SSRIs) (n=11; 78.6%), mirtazapine (n=2, 14.3%), and amitriptyline (n=1, 7.1%). RESULTS: Twelve (85.7%) patients (nine remitters, three partial responders) received at least 4 weeks of atomoxetine treatment. The remaining two (partial responders) discontinued atomoxetine within 1-3 days due to increased anxiety. The brief fatigue inventory (BFI) and Clinical Global Impressions Scale (CGI) were administered when atomoxetine was first prescribed, and following 4-10 weeks of treatment (mean of 5.4+/-1.8 weeks). There was a significant decrease in BFI scores (41.9+/-14.9 versus 24.3+/-13.4, p=0.0015), and HDRS-17 scores (6.2+/-2.4 versus 3.5+/-2.8, p=0.0466), but not CGI-S scores (1.3+/-1.4-1.0+/-0.0, p=0.08) following treatment with atomoxetine. 5/12 (41.6%) patients had a 50% or greater decrease in BFI scores. All 12 patients were remitters at follow-up. The mean atomoxetine dose was 42.8+/-10.6 mg. Side effects included insomnia (n=6), increased anxiety (n=3), nausea (n=1) and dry mouth (n=1). CONCLUSIONS: Although preliminary, these results suggest a possible augmentation role for atomoxetine when used in conjunction with conventional antidepressants for residual fatigue in MDD. Prospective as well as controlled studies are necessary to further explore the role of atomoxetine augmentation in MDD.     

Influence of mirtazapine on urinary free cortisol excretion in depressed patients

Mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on urinary free cortisol (UFC) excretion was investigated in depression. Twenty patients (six men, 14 women) suffering from major depression according to DSM-IV criteria were treated with mirtazapine for 3 weeks. The patients received 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg mirtazapine per day from day 2 to the end of the study (day 21). UFC excretion was measured before treatment (day 1), at the beginning (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Urine samples were collected from 08:00 to 08:00 h the following day. On the days of urine sampling, the severity of depressive symptoms was assessed using the 21-item version of the Hamilton Rating Scale for Depression (21-HAMD). There was a significant reduction of UFC excretion during 3-week mirtazapine therapy, which was already obvious after the first day of treatment (day 0). However, there were no significant across-subjects correlations between UFC reduction and decrease in 21-HAMD sum scores. Apparently, the mirtazapine-induced rapid reduction of cortisol secretion in depressed patients is not necessarily correlated with a favorable therapeutic response.     

Clinical significance of sleep EEG abnormalities in chronic schizophrenia

This study aimed to investigate the relationship between measures of clinical symptom severity and sleep EEG parameters in a relatively diagnostically homogeneous group of patients with schizophrenia. We obtained sleep EEG data in 15 drug-free inpatients who met DSM-IV-R criteria for schizophrenia, undifferentiated type, with 15 age- and sex-matched normal controls over two consecutive night polysomnographic recordings. Clinical symptoms were assessed by the Positive and Negative Symptom Scale (PANSS) and Hamilton Rating Scale for Depression. Characteristic features of sleep disturbance were seen in patients with schizophrenia: profound difficulties in sleep initiation and maintenance, poor sleep efficiency, a slow wave sleep (SWS) deficit, and an increased REM density. SWS was inversely correlated with cognitive symptoms. REM density was inversely correlated with positive, cognitive, and emotional discomfort symptoms as well as PANSS total score. Our data demonstrate that drug-free patients with chronic undifferentiated type schizophrenia suffer from profound disturbances in sleep continuity and sleep architecture. Both the SWS deficit and cognitive impairment found in schizophrenics in this study may relate to similar underlying structural brain abnormalities.     

Simultaneous panic and depressive disorders: clinical and sleep EEG correlates

Panic and depressive symptoms occur simultaneously in many depressed patients. To study the frequency of this association and to determine whether patients with simultaneous panic and major depression differed from those with only major depressive disorder (MDD) in clinical features and in sleep electroencephalographic (EEG) variables, we evaluated a total sample of 336 patients with MDD. Fifty-eight (17%) had both panic and MDD; 50 had complete data and were matched for age and severity of illness with other patients having only MDD. Patients with simultaneous panic and depression had significantly higher ratings for psychic and somatic anxiety, and rapid eye movement (REM) latencies approximating normal values. Patients with only MDD (without panic disorder) rated significantly higher in guilt feelings and had shorter REM latencies. Our results suggest that the simultaneous occurrence of panic and depression is relatively frequent, is accompanied by differences in sleep EEG variables, and may have implications for treatment.     

Effects of mirtazapine on sleep polygraphic variables in major depression

Mirtazapine, a noradrenergic and specific serotonergic antidepressant(NaSSA), was administered on a flexible schedule in a sample of 17 drug-free patients meeting DSM-IV criteria for a major depressive episode. Sleep polygraphic recordings were performed before and during acute and chronic treatment. Severity of depression and subjective assessment of changes within different aspects of sleep were also evaluated. During the acute administration (first 2 days), mirtazapine significantly increased total sleep time, sleep efficiency, stage II, stage rapid eye movement and slow-wave sleep percentages, and decreased sleep latency and stage awake percentage. These effects persisted after 5 weeks of treatment. Subjectively, mirtazapine induced an improvement of sleep. This open, noncontrolled study suggests that mirtazapine ameliorates the sleep disturbances encountered in depressed patients both objectively and subjectively.     

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.     

Cholinergic REM induction response: separation of anxiety and depression

Five groups of subjects underwent EEG sleep recordings, arecoline rapid eye movement (REM) induction response testing, and Schedule for Affective Disorders and Schizophrenia (SADS) interview. Group I: 20 patients with primary major depressive disorder (MDD) (endogenous) without any coexisting anxiety disorder; Group II: 19 primary MDD (endogenous) patients with secondary panic, GAD, or phobic disorders; Group III: 18 patients with primary anxiety disorder without coexisting MDD; Group IV: 14 patients with primary anxiety plus secondary MDD; Group V: 26 normal controls. Modified Research Diagnostic Criteria (RDC) were used for diagnosis, based on the SADS interview. There was considerable overlap of SADS scaled scores between patient groups, which is consistent with a heterogeneous clinical presentation of depressive and anxiety states. REM latency was significantly shorter in patients with primary MDD (without anxiety) as compared with that in patients with primary anxiety (no MDD) and normals. Arecoline REM induction response time was significantly shorter in both primary affective groups (I and II) as compared with primary anxiety (no MDD) patients and normal controls. REM latency and arecoline REM induction time was not significantly different between the primary anxiety groups (III and IV) and normals. The study highlights the use of biological markers in differentiating between clinical syndromes confounded by mixed or overlapping phenomenology.     

Sleep and body mass index in depressed children and healthy controls

ObjectiveHigher body mass index (BMI) has been associated with more sleep disturbance and depressive symptoms, but the combined effects of depression and BMI on sleep have not been studied in children. This study evaluated the relationship between BMI and polysomnography in children with major depressive disorder (MDD), compared to healthy controls (HCs).MethodThe sample of 104 subjects included 72 children, 8–17 years old, with MDD and 32 similarly aged HCs with no personal or family history of psychopathology. BMI was adjusted using the CDC formula for percentiles by age. Subjects were categorized as (1) normal weight (5–84th percentile) or (2) high weight, which included at risk of overweight and overweight (?85th percentile). All analyses were adjusted for sex and Tanner maturational stage scores.ResultsIn the MDD group only, higher BMI was significantly correlated with decreased sleep efficiency, decreased percentage of rapid eye movement sleep (REM%), and higher percentage of time spent awake and moving (TSPAM). In the HC group only, higher BMI correlated with higher total sleep time. Multivariate analyses revealed significant interactions between the BMI and diagnostic groups for several REM sleep parameters, such that high-weight children from the HC and MDD groups had increases and decreases in REM sleep, respectively. TSPAM increased in the high-weight MDD group, but decreased in the high-weight HC group.ConclusionsAlthough limited by small sample size, these findings suggest that children and adolescents with MDD and a high BMI have more fragmented sleep than other children. The increased REM sleep patterns observed with MDD in this and other studies normalized in high-weight children with MDD. Prevention and treatment strategies should target both sleep and weight as factors that can potentially influence the development and course of MDD.     

Cholinergic REM sleep induction response correlation with endogenous major depressive subtype

We compared central cholinergic responsiveness (using the latency to induction of rapid eye movement sleep after arecoline challenge as a response marker) in 90 subjects: patients with major depressive disorder (MDD) (n = 53), nonaffective psychiatric controls (n = 17), and normal controls (n = 20). MDD patients as a whole showed a supersensitive cholinergic response compared to nonaffective patients and normal subjects. Further analysis indicated a strong association between cholinergic supersensitivity and endogenous subtype of MDD, including a significant correlation with specific endogenous features such as distinct quality of mood, anhedonia, lack of reactivity, and agitation. Unlike rapid eye movement (REM) latency (a more conventional physiological marker), cholinergic sensitivity did not correlate with age or severity of illness but only with the presence of endogenous features. Previously described sleep physiological correlates such as REM latency and REM density of the first REM period also distinguished between endogenous and nonendogenous MDD. There was a statistically significant correlation between REM latency and arecoline REM induction response.     

Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia

BACKGROUND: Sleep complaints are common in patients with major depressive disorder (MDD). Both MDD and antidepressant drugs characteristically alter objective sleep measures. This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia. METHOD: Patients (N = 19) received initial baseline polysomnography evaluations over 2 consecutive nights. Subjects were randomly assigned to either fluoxetine (20-40 mg/day) or mirtazapine (15-45 mg/day) treatment for an 8-week, double-blind, double-dummy treatment trial. Single-night polysomnograms were conducted at weeks 1, 2, and 8, with depression ratings assessed at baseline and weeks 1, 2, 3, 4, 6, and 8. Statistical analysis was performed by repeated-measures analysis of variance followed by Dunnet's post hoc analyses. RESULTS: Patients receiving mirtazapine (N = 8) had significant improvement in objective sleep physiology measures at 8 weeks. Improvements in sleep latency, sleep efficiency, and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment. No significant changes in sleep continuity measures were observed in the fluoxetine group (N = 11). Both groups improved clinically in mood and subjective sleep measures from baseline, with no differences between groups. CONCLUSION: These data demonstrate the differential effects of mirtazapine and fluoxetine, with significant improvement in favor of mirtazapine, on objective sleep parameters in MDD patients with insomnia.