The Expert Consensus Guideline Series. Treatment of depression in women.

OBJECTIVES: Women constitute two-thirds of patients suffering from common depressive disorders. The treatment of depression in women is therefore a substantial public health concern. High-quality, empirical data on depressive disorders specific to women are limited. As a result, there are no comprehensive evidence-based practice guidelines on the best treatment approaches for these illnesses. We conducted a consensus survey of expert opinion on the treatment of 4 depressive conditions specific to women: premenstrual dysphoric disorder (PMDD), depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause. METHOD: After reviewing the literature and convening a work group of leading experts, we prepared a written survey covering a total of 858 treatment options in 117 specific clinical situations. Depression severity (mild to severe) was specified for most clinical situations. Treatment options included a broad range of pharmacological, psychosocial, and alternative medicine approaches. Most options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. We identified 40 national experts, 36 (90%) of whom completed the survey. Consensus on each option was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 76% of the options, with greater consensus in situations involving severe symptoms. For women with severe symptoms in each of the 4 central disorder areas we asked about, the first-line recommendation was for antidepressant medication combined with other modalities (generally psychotherapy), paralleling existing guidelines for severe depression in general populations. For milder symptoms in each situation, the panel was less uniform in recommending antidepressants. For the initial treatment of milder symptoms, the panel either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (in conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) as a class were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation. CONCLUSIONS: The experts reached a high level of consensus on the appropriateness of including both antidepressant medication, specifically SSRIs, and nonpharmacological modalities in treatment plans for severe depression in 4 key clinical situations unique to women. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data in comparing modalities with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

Treatment of depression in women: a summary of the expert consensus guidelines.

Women constitute two-thirds of patients suffering from common depressive disorders, making the treatment of depression in women a substantial public health concern. However, high-quality, empirical data on depressive disorders specific to women are limited, and there are no comprehensive evidence-based practice guidelines on the best treatments for these illnesses. To bridge the gap between research evidence and key clinical decisions, the authors developed a survey of expert opinion concerning treatment of four depressive conditions specific to women: premenstrual dysphoric disorder, depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause. The survey asked about 858 treatment options in 117 clinical situations and included a broad range of pharmacological, psychosocial, and alternative medicine approaches. The survey was sent to 40 national experts on women's mental health issues, 36 (90%) of whom completed it. The options, scored using a modified version of the RAND Corporation's 9-point scale for rating appropriateness of medical decisions, were assigned one of three categorical rankings-first line/preferred choice, second line/alternate choice, third line/usually inappropriate-based on the 95% confidence interval of each item's mean rating. The expert panel reached consensus (defined as a non-random distribution of scores by chi-square "goodness-of-fit" test) on 76% of the options, with greater consensus in situations involving severe symptoms. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. The authors summarize the expert consensus methodology they used and then, for each of the four key areas, review the treatment literature and summarize the experts' recommendations and how they relate to the research findings. For women with severe symptoms in each area we asked about, the first-line recommendation was antidepressant medication combined with other modalities (generally psychotherapy). These recommendations parallel existing guidelines for severe depression in general populations. For initial treatment of milder symptoms in each situation, the panel was less uniform in recommending antidepressants, and either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (during conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation. In evaluating many of the treatment options, the experts had to extrapolate beyond controlled data in comparing treatment options with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women, and can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

Evaluating and managing premenstrual syndrome.

Premenstrual syndrome (PMS), a common disorder in women, refers to physical and/or mood symptoms that appear predictably during the latter half of the menstrual cycle, last until menses begin, and are absent during the early part of the menstrual cycle. A diagnosis of PMS requires that the symptoms be severe enough to affect a woman's ability to function at home or in the workplace or in her relationships with others. Diagnostic assessment entails a thorough medical and psychiatric history and prospective daily ratings. Disorders such as major depression, anxiety, hypothyroidism, and diabetes must be excluded before a diagnosis of PMS can be considered. Treatment strategies include either eliminating the hormonal cycle associated with ovulation or treating the symptom(s) causing the most distress to the patient. Medical therapies are available for both treatment approaches but should be initiated only after behavioral measures have failed; the physician must also carefully weigh the severity of symptoms against the potential for adverse effects of treatment.

Premenstrual syndrome. Identification and management.

Premenstrual syndrome is a legitimate illness consisting of the cyclic recurrence of symptoms (physical, mental and behavioural) in the late luteal phase of the menstrual cycle of sufficient severity to require treatment. The syndrome has a yet unknown aetiology, an uncertain and variable course, and an unidentified family history. Methods are available for diagnosis including obtaining a reliable history, thorough physical and mental examinations, laboratory tests to exclude other possible causes of symptoms, and daily prospective symptom ratings to confirm symptom patterns. Because there is no known aetiology, treatment consists of symptom management of the specific symptoms experienced, based on prospective symptom ratings.

Pediatricians and sleep disorders: training and practice.

OBJECTIVE: A series of studies were conducted to investigate pediatricians' training, knowledge, and practices regarding sleep and sleep disorders in children and adolescents. METHOD AND RESULTS: Study 1, a national survey of 156 pediatric residency programs, found that pediatricians receive a mean of 4.8 hours of instruction on sleep and sleep disorders, although the mode and median hours of instruction is 0 hours. In study 2, 88 pediatricians completing a questionnaire concerning general knowledge about sleep disorders in children and adolescents received a mean score of 71.8% (range, 40% to 93%). Pediatricians appear to know the most about developmental issues and sleep hygiene and the least about specific disorders such as narcolepsy and parasomnias. In the third study, 183 pediatricians were surveyed about their actual beliefs and practices regarding young children's sleep problems. Together, those surveyed reported that approximately 25% of their patients experience some type of sleep problem. Most pediatricians recommend behavioral interventions, although 14.8% of pediatricians report prescribing pharmacological treatments, and 48.9% inform parents that their child is likely to outgrow the problem. CONCLUSIONS: The results of these studies support the need for more education in sleep and sleep disorders in children and adolescents within medical schools, pediatric residency programs, and the practicing pediatric community.

Pharmacologic strategies for managing premenstrual syndrome.

The diagnosis and pharmacologic management of premenstrual syndrome (PMS) are reviewed. PMS refers to physical or affective symptoms that appear during the latter half of the menstrual cycle, remit during menses, and affect the woman's relationships or ability to function. Pharmacologic treatments proposed for PMS include (1) hormonal treatments that alter the menstrual cycle, (2) hormonal treatments based on specific proposed etiologies, (3) drugs that affect fluid balance, (4) inhibitors or precursors of prostaglandins, (5) nutritional supplements, (6) psychotropic medications, and (7) nonprescription preparations. The menstrual cycle can be manipulated with transdermal estrogen and cyclic oral progesterone, oral contraceptives, danazol, or gonadotropin-releasing hormone agonists with steroid hormone replacement. Psychological symptoms may be treated with fluoxetine, clomipramine, or alprazolam. Patients may be given a diuretic for fluid retention; bromocriptine, tamoxifen, or danazol for mastodynia; and nonprescription analgesics for headaches. PMS can be managed through (1) a symptom-oriented management approach or (2) modification of the menstrual cycle. Pharmacotherapy should be initiated only after simpler measures have failed, and the medication must be chosen carefully, with the severity of the impairment weighed against adverse effects of the treatment.

Cognitive and motor performance of narcoleptic and normal subjects living in temporal isolation.

Six unmedicated narcoleptic subjects and nine normal controls lived in a temporal isolation laboratory for 18-22 days. They were permitted to "free-run" for the last 9-13 days. Brief cognitive and motor performance tests were repeated on average six times per subjective day. They consisted of serial search, complex verbal reasoning tasks and manual dexterity of each hand. Only minor differences in performance were found between the narcoleptic subjects and controls. Narcoleptic subjects showed mild impairment of accuracy on the search task that could be explained by occasional lapses and an afternoon dip in performance. Narcoleptic subjects also tended to perform some tasks more slowly, but the group differences were not significant. Neither speed nor accuracy of performance of narcoleptic subjects decreased over the course of the experiment. By one standard of performance, therefore, all or nearly all of the sleep need of these subjects was met by the sleep they obtained in the laboratory. That amount, in turn, did not exceed the total sleep obtained by the normal controls. Significant time-of-day effects were found in narcoleptic subjects for speed of verbal reasoning (progressive slowing over the course of the day), manual dexterity (fluctuations in speeds) and accuracy of serial search (afternoon dip). These variations in performance could not be attributed to changes in core body temperature or to occurrences of naps or meals.

Age-related differences in recovery from simulated jet lag.

Six healthy young men and eight early middle-aged men were isolated from environmental time cues for 15 days. For the first 6-7 days (one or two nights adaptation, four nights baseline), their sleep and meals were scheduled to approximate their habitual patterns. Their daily routines were then shifted 6 hours earlier by terminating the sixth or seventh sleep episode 6 hours early. The new schedules were followed for the next 8 or 9 days. Important age-related differences in adjustment to this single 6-hour schedule shift were found. For the first 4-day interval after the shift, middle-aged subjects had larger increases of waking time during the sleep period and earlier termination of sleep than young subjects. They also reported larger decreases in alertness and well-being and larger increases in sleepiness, weariness and effort required to perform daily functions. The rate of adjustment of the circadian core temperature rhythm to the new schedule did not differ between groups. These results suggest that the symptoms reported by the middle-aged subjects may be due mainly to difficulty maintaining sleep at early times of the circadian day. The compensatory response to sleep deprivation may also be less robust in middle-aged individuals traveling eastbound.

High nocturnal body temperature in premenstrual syndrome and late luteal phase dysphoric disorder.

OBJECTIVE: Because women with late luteal phase dysphoric disorder (LLPDD) experience symptomatic affective states predictably, they can be studied to determine whether there are biological findings related solely to the clinically symptomatic state. The authors sought to answer the question, Does body temperature change with affective state? METHOD: The core body temperature and motor activity patterns of 10 women with premenstrual syndrome (PMS), six of whom also met criteria for LLPDD, and no other psychological or medical illness were compared to those of six women with chronic, noncyclic dysphoria and six asymptomatic comparison women at four phases of the menstrual cycle. RESULTS: The nocturnal temperatures of the women with PMS/LLPDD were significantly higher than those of the comparison subjects across the entire menstrual cycle, but there were no differences in nocturnal activity levels. The women with noncyclic dysphoria had a mean nocturnal temperature in the follicular phase as high as that of the women with PMS/LLPDD. The temperatures of all women were higher in the luteal phase than in the follicular phase. CONCLUSIONS: These findings suggest that in the future investigators should document menstrual cycle phase in all female subjects and, when studying body temperature, should carefully monitor symptomatic state in comparison subjects.

Premenstrual syndrome.

Because researchers are still seeking the cause of PMS, we cannot recommend a single treatment approach that will work satisfactorily with all women who have the syndrome. Investigators have made progress, however, toward defining and diagnosing the condition. We also can help women whose lives are disrupted each month by prescribing specific approaches to symptom management.

The timing of bedtime and waketime decisions in free-running subjects.

Twelve "free-running" temporal isolation studies were performed using healthy human subjects aged 20-81 years (4 males, 8 females). Circadian rhythms were measured in subjective alertness (using a visual analogue scale technique) and rectal temperature. In all 12 subjects best fitting rhythm period were found to be shorter for rectal temperature (mean = 24.3 hours) than for subjective alertness (mean = 24.8 hours). Both rhythms were predictive of bedtime and waketime decisions. Bedtime decisions tended to cluster on the falling arm of the temperature and alertness cycles (modal times = 120 degrees (temperature) and 140 degrees (alertness) after acrophase); waketime decisions on the rising arm (modal times = 240 degrees (temperature) and 300 degrees (alertness) after acrophase). When this pattern was violated, sleep episodes were significantly more variable in length and disturbed by intruding wakefulness.

Circadian determinants of subjective alertness.

Four healthy male subjects each experienced a temporal isolation experiment lasting several months. During part of each experiment (2-5 weeks), the subject's entire imposed daily routine (including light-dark, rest-activity, and meal routines) was either stretched (two subjects: T = 25.8 hr, 26.0 hr) or reduced (two subjects: T = 22.8 hr, 23.1 hr) to beyond the range of entrainment of the endogenous circadian pacemaker (ECP), which then ran at a different period (tau). Subjective alertness was measured approximately three times per hour (during wakefulness), using a computerized visual analogue scale technique. Circadian rhythms in subjective alertness were then plotted both at tau, the period length of the ECP, and at T, the period length of the imposed sleep-wake cycle (SWC) and light-dark cycle. At tau, the alertness rhythm was closely in phase with the temperature rhythm. At T, the alertness rhythm showed an "inverted-U" function with a peak toward the middle of the subjective day, upon which was superimposed a "postlunch dip" for one subject. Thus, subjective alertness would appear to be under the control fo both ECP and SWC mechanisms, which combine to produce the composite time-of-day function normally observed in a diurnal setting.

Removal of temporal constraints in the middle-aged and elderly: effects on sleep and sleepiness.

Ten healthy middle-aged and elderly subjects (44-81 years old; 4 men and 6 women) were studied in time isolation experiments involving: (a) entrainment to the subject's habitual routine (EN condition) and (b) removal of all temporal constraints or "free-running" (FR condition) with the subjects able to choose their own bed and meal times. Subjective day lengths and circadian temperature cycle periods were longer under FR than under EN, but not by an equal amount. Perhaps as a consequence, although time-in-bed (TIB) fractions were greater under FR than under EN, actual sleep fractions were not, reflecting a decline in sleep efficiency. Neither was there an increase in slow-wave sleep (SWS) under FR compared with EN. Daytime subjective alertness did, however, increase upon release into FR, also showing a slightly earlier peak than that observed under the EN condition. The results point to the need to regard sleep and sleepiness as rhythmic, as well as homeostatic, processes.