To examine the efficacy of an early minimal cognitive behavioral therapy (CBT) intervention for insomnia in patients with cancer

The treatment consisted of self-help CBT provided with written materials and three phone consultations. Participants completed a quiz after each booklet was read and were asked to maintain a daily sleep diary. Control patients did not receive any intervention. The study was conducted over six weeks. Study measures were obtained at baseline, at the end of six weeks, and three and six months later. Participants were paid after each assessment was completed.

• N = 35  
• MEAN AGE = 56.9 years (SD = 10 years)
• MALES: 7.9%, FEMALES: 92.1%
• KEY DISEASE CHARACTERISTICS: Most had breast cancer; various other types included
• OTHER KEY SAMPLE CHARACTERISTICS: 60% were married, 65.8% were in current treatment for cancer with radiation therapy and/or chemotherapy

• SITE: Single site  
• SETTING TYPE: Not specified    
• LOCATION: Canada

• PHASE OF CARE: Multiple phases of care

Randomized, controlled trial

• Insomnia Interview Schedule (IIS)
• Insomnia Severity Index (ISI)
• Sleep diary
• Hospital Anxiety and Depression Scale (HADS)
• Multidimensional Fatigue Inventory (MFI)
• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)
• Dysfunctional Beliefs and Attitudes About Sleep–Short Form (DBAS-SF)
• Sleep Behaviors Questionnaire (SBQ)

There were significant effects over time by study group on ISI scores in favor of the CBT intervention at six weeks (p < 0.001), and there were improvements in all sleep variables with effect sizes (d) ranging from 0.46–1.34. Control patients also showed improvements. There were no significant changes from the six-week to six-month time point in either group. Those in the CBT group had a reduction in hypnotic dosage (d = 0.40). There were significant improvements in anxiety scores (p < 0.001) in the CBT group at six weeks. Depression declined significantly in both groups. No significant effect on fatigue was found. A greater proportion of CBT patients achieved a sleep efficiency level greater than or equal to 85% (p = 0.01). More than 97% of patients completed the materials, and 91.2% completed the quiz on average.

The brief CBT intervention used here was effective in improving insomnia and anxiety among patients with cancer.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: Use of hypnotics was not described after baseline

CBT interventions are effective in treating sleep–wake disturbances and psychological issues. This study demonstrated that the provision of a CBT approach via booklets and quizzes on the CBT for sleep content with follow-up and counseling by phone was an effective way to deliver the intervention. Although this sample size was small, it did approximate the size required from a power analysis. This approach to providing a CBT intervention can be practical and cost-effective. However, significant effects were only seen during the active study period, and effects were not shown to endure long-term.

To determine the efficacy of low‐level laser treatment (LLLT) in the prevention and treatment of radioinduced oral mucositis in patients with oral and oropharynx cancer

Patients were randomized into two groups. Group 1 received 660 nm/15 mW/3.8 J/cm² spot size 4 mm² LLLT, and Group 2 received 660 nm/5 mW/1.3 J/cm² spot size 4 mm² LLLT, both beginning on the first day of radiation. In both groups, LLLT application was done daily for five consecutive days per week starting on the first day of radiation therapy. Prior to the study, all patients underwent oral care, including an oral examination, preventive dental treatment, instructions for oral care during radiation therapy, and prescription mouthwashes and fluoride treatment. Randomized sample selection was based on the eligibility criteria that each patient was diagnosed with cancer of the oral cavity or oropharynx and treated with radiation therapy.

• The study reported on a sample of 54 patients.
  • The mean patient age in group 1 was 57.1 (SD = 12.8) with a range of 22–94 years.
  • The mean patient age in group 2 was 58.1 (SD = 10.9) with a range of 35–79 years.
• The sample was 66% male and 34% female.
• Patients were included in the study if they received conventional, three-dimensional conformal radiotherapy or intensity-modulated radiation therapy with doses in facial fields equal to or greater than 4,000 cGy exclusively or associated with chemotherapy.

This was a single-site study conducted in an inpatient setting at Hospital A.C. Camargo, Sao Paulo Brazil.

Patients were undergoing the active treatment phase of care.

This was a prospective, randomized, double-blind study.

• The National Cancer Institute (NCI) classification criteria for oral mucositis was used.
• The World Health Organization (WHO) classification criteria for oral mucositis was used.
• A visual analog scale was used for pain evaluation, with 0 equal to no pain and 10 equal to maximum pain.

Group 1 had a delay in presentation with oral mucositis compared to Group 2 (13.5 days to 9.8 days, respectively). Group 2 presented with a higher grade of mucositis as compared to Group 1, and Group 2 reported higher overall pain scores.

This study reported a delay in development of mucositis, a decrease in severity of mucositis, and a decrease in pain scores with the group that received the higher dose of LLLT during treatment for oral or oropharynx cancer.

• The sample size was small, with fewer than 100 patients.
• Other limitations of the study included the fact that the incidence of oral mucositis may be affected by the location of primary tumors in different sites of the oral cavity and oropharynx.
• The study also did not take into account that some patients are reluctant to report pain symptoms, and no differences were found between the two groups in the reduction of analgesic administration.

Further studies are necessary to define dose, application time, and number of sessions needed for laser therapy in prevention and management of oral mucositis.

PHASE OF CARE: Multiple phases of care

Of 677 articles, 22 were selected for a full review. Following consensus, only two were found eligible for key question 1. In one RCT, mianserin had significant antidepressant effects compared to a placebo. In the second RCT, desipramine and paroxetine no were more efficacious than a placebo. Of 1,149 articles, 52 articles were selected for full review for key question 2, but none met the inclusion criteria.

The results of this systematic review highlight the paucity of RCTs evaluating the efficacy and tolerability of antidepressants for the treatment of MDDs in women with breast cancer. No RCTs for psychotherapeutic approaches were identified for this systematic review, emphasizing the lack of data for the treatment of MDDs in patients with breast cancer. Further research is needed on the treatment of MDDs based on clinical experience.

• The results of the two eligible RCTs were mixed.
• They had small samples and significant risk of bias.
• The authors did not include unpublished results, and the review only focused on depression-related outcomes.

Psychological distress is an unmet need in patients with breast cancer and needs to be researched further.

To evaluate the effect of prayer on the anxiety of patients with cancer receiving chemotherapy

Participants were interviewed about sociodemographic and clinical characteristics. They were then given the Duke University Religion Index (DUREL) to measure three dimensions of religiosity. Then, they applied the State-Trait Anxiety Inventory (STAI-S and STAI-T). Preintervention data collection included a repeat STAI-S and a saliva and vital sign measurement taken by the same examiner. The prayer intervention was then conducted by the researcher. The intervention consisted of a specific Christian prayer delivered in an audio recording over 11 minutes. Thirty minutes after prayer, the STAI-S and salivary sample and vital signs were repeated. The control group received the same protocol with no prayer intervention.

• N = 20  
• AGE = > 18
• MALES: 75%, FEMALES: 25%
• KEY DISEASE CHARACTERISTICS: Cancer diagnosis
• OTHER KEY SAMPLE CHARACTERISTICS: Receiving continuous IV chemotherapy; willing to receive prayer; and clinically stable

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Minas Gerais, Brazil

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care and palliative care 

Quasi-experimental, pre- and postintervention study with a control group

• State-Trait Anxiety Inventory (STAI): Two-part STAI-T and STAI-S
• Duke University Religion Index (DUREL)
• BioEstat 5.0 program used to chart and analyze results
• The Wilcoxon signed-rank test compared state anxiety levels, salivary cortisol, blood pressure, and heart and respiratory rate pre- and postintervention.

The sample revealed a high level of religiosity. Anxiety state was influenced by nonorganizational religious activity (p = 0.01), and a correlation with age group (p = 0.01) existed. The anxiety profile measure before the intervention displayed moderate levels of anxiety. A comparison of pre- and postintervention means demonstrated modified values for state anxiety, blood pressure, and respiration rate. The STAI-S showed reduced anxiety after prayer at each moment. Values related to anxiety levels and vital signs were reduced after each intervention and for all three repetitions of pre- and postintervention observation (anxiety levels [p < 0.00], respiratory rate [p = 0.04], blood pressure [p = 0.00]).

The authors concluded that prayer is effective in reducing the anxiety of patients receiving chemotherapy. Evaluating anxiety by measuring vital signs is recommended as a simple technique. The nursing application of a standardized prayer protocol in the clinical environment addresses patients' spiritual dimensions and could reduce anxiety.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Findings not generalizable
• Questionable protocol fidelity
• Other limitations/explanation: The researcher was the creator, administrator, and evaluator of the intervention.

The spiritual care of patients with cancer is an important dimension of care. Continued research on the effectiveness of prayer for patients who value prayer can be meaningful in reducing anxiety.

To examine the effectiveness of Camelia Sinensis leaf extract to prevent oral mucositis (OM) in patients undergoes autologous and allogeneic stem cell transplant (SCT)

Patients undergoing SCT randomly were assigned to the experimental group or the control group. Patients in the experimental group received 20 ml of Baxidil Onco^® four times a day from day -1 to day +30, in addition to standard prophylactic measures. Baxidil Onco is composed of Camelia Sinensis leaf extract and palmitoyl hydrolyzed wheat protein. Patients in the control group received standard prophylactic measures only. As a standard measure, all patients received mouthwashes with 0.9% saline/sodium bicarbonate solution, 0.12% chlorhexidine, and amphotericin B. 

Patients with grade 2 or higher OM additionally received oral care with sponges or soft gauzes. All patients also received 400 mg acyclovir twice daily from day -3 to 16 weeks, 400 mg fluconazole once daily, 500 mg ciprofloxacin once daily, and 960 mcg co-trimoxazole twice daily until day of transplant.

• N = 60; 28 in the experimental group, 32 in the control group
• AGE RANGE: 21–72 years
• MALES: 65%, FEMALES: 35%
• KEY DISEASE CHARACTERISTICS: Diagnoses were multiple myeloma (n = 23), B-cell non-Hodgkin lymphoma (n = 14), acute myeloblastic leukemia (n = 10), acute lymphoblastic leukemia (n = 7), chronic lymphocytic leukemia (n = 2), primary myelofibrosis (n = 1), myelodysplastic syndrome (n = 1), paroxysmal nocturnal myelodysplastic (n = 1), and Hodgkin lymphoma (n = 1).

• SITE: Single site
• SETTING TYPE: Inpatient
• LOCATION: Italy

PHASE OF CARE: Active antitumor treatment

• Randomized, non-blinded, experimental study

• World Health Organization (WHO) Oral Toxicity Scale
• Greene and Vermillion's Oral Hygiene Index (OHI-S)
• Total morphine use also was recorded.

OM was found in 81.2% of patients in the control group and 50% of patients in the study group (p = 0.022). Incidence rates for patients undergoing allogeneic transplant were 89% in the control group and 64% in the study group. Moderate to severe mucositis was more prevalent in the control group (56.2%) than in the study group (25%) (p = 0.029). No statistically significant results were found in incidence of severe mucositis (p = 0.16). Total requirement of morphine was 1,300 mg for the study group and 2,880 mg in the control group. However, this result was not statistically examined.

Baxidil Onco may be effective in reducing OM in patients undergoing hematopoietic SCT. A caution may apply for patients with wheat allergy. More patients were undergoing allogeneic transplant in the control group than in the study group. Because incidence of mucositis generally is higher in allogeneic hematopoietic SCT, this presents a potential bias. Further study with larger sample sizes is necessary.

• Small sample (< 100)
• Risk of bias (lack of blinding and sample characteristics)

Baxidil Onco may help reduce OM for patients undergoing hematopoietic SCT. However, further study with larger sample sizes is necessary for this to be used as a standard of practice. 

To test the feasibility and effectiveness of a brief behavioral sleep intervention for family caregivers of persons with advanced stage cancer

Each caregiver received an Actigraph on the wrist of the dominant hand and was asked to wear it for the next three days. During this time, the caregiver completed a sleep log to illustrate times out of bed, time to bed, awakening and out of bed, and times of disturbance. At week two, intervention group caregivers (n = 15) received the CASI (author developed sleep intervention), and the attention control group caregivers received body mechanics information and training. All caregivers completed the Pittsburgh Sleep Quality Index (PSQI), Center for Epidemiological Studies—Depression Scale (CES-D), and Caregiver Quality of Life Index—Cancer (CQOLC) at week three and provided sleep log and Actigraph data. A booster CASI session was delivered to the intervention group at week four, and the attention group received a booster of the body mechanics material. The intervention incorporated stimulus control, relaxation therapy, cognitive therapy, and sleep hygiene. Participants were educated on sleep promotion techniques within the context of caregiving. Measurements of all study variables from both groups occurred in week five and two, three, and four months post-baseline.

• The sample included 30 participants.
• The mean age of the sample of 30 family caregivers was 53 years (age range 21–85 years).
• Females: 63% (both intervention and control groups) (n = 19)
• Males: 27% (both intervention and control groups) (n = 11)
• Participants had multiple cancer diagnoses, were at end of life, and were not in a hospice program.
• Inclusion criteria required caregivers to be at least 21 years of age; identify themselves as family caregivers; have reported difficulty in beginning and maintaining sleep or non-restorative sleep for at least one month; and live with patients whose caregivers assessed them as having advanced stage cancer diagnoses.
• Most caregivers were spouses (57%) or adult children (30%) and provided care for a mean length of 17 hours per day.
• Eighty-seven percent of caregivers were Caucasian, and 13% were Hispanic.

• Multi-site
• Home
• Central Texas USA

A repeated measures experimental design was used.

• Pittsburgh Sleep Quality Index (PSQI) (used to measure caregiver sleep quality)
• Actigraph sleep watch (used to measure sleep patterns [latency, duration, efficiency, and wake after sleep onset])
• Sleep logs
• Center for Epidemiological Studies—Depression Scale (CES-D) (used to measure caregiver depression symptoms)
• Caregiver Quality of Life Index—Cancer (CQOLC) (used to measure caregiver quality of life)

Pearson product correlations reported on how sleep duration and efficiency were “strongly negatively associated” with caregiver depression and quality of life over time; however, actual statistical results were not provided in this report. Overall sleep quality (PSQI) and sleep latency were strongly and consistently correlated with caregiver depression and quality-of-life scores over time. Quality-of-life scores were strongly and consistently positively correlated with depressive symptoms over time, according to the author. Caregiver quality of life and self-reported sleep quality improved for both groups over the duration of the study. Intervention caregivers showed greater improvements in PSQI total scores than did control caregivers at each time measurement. The difference between groups in PSQI score was only statistically significant at month four in the study (p = 0.03), in favor of the intervention group.

Delivery of a home-based caregiver sleep intervention may be helpful for caregivers who report sleep disturbances that dramatically influence their personal quality of life and ability to provide care to a family member with cancer. This intervention appears to be feasible and can be tailored to the caregiver.

• The sample had less than 100 participants.
• The limited ethnic representation in sample limits generalizability of findings.
• The limited sample size also affects the use of more powerful statistical analysis that would support efficacy of the intervention. 
• It is unclear whether randomization occurred for the caregiver group assignment.
• The author states a number of significant results; however, the actual data and statistics for these are not all provided.

Findings suggest that an intervention to improve caregiver sleep quality may be helpful and that poor sleep quality is associated with lower quality of life and depressive symptoms.

To (a) evaluate the feasibility (recruitment and retention, instrumentation, and intervention administration) and effectiveness of a brief behavioral Caregivers Sleep Intervention (CASI) that addressed the specific needs and sleep goals of family caregivers of persons with cancer, and (b) determine the effectiveness of  CASI in improving caregivers’ sleep quality, depressive symptoms, and quality of life

The Caregivers Sleep Intervention (CASI) had two sessions. The initial CASI session (week 2 of the study) lasted one hour and provided knowledge, guided participants in self-assessment of maladaptive habits affecting their sleep quality, and assisted participants to develop personal sleep and relaxation goals. In study week 5, a second one-hour CASI session (booster) reviewed the information provided in the initial session and rated personal sleep and relaxation goal achievement. Topics covered were (a) the importance of sleep and sleep \"myth busting,\" (b) stimulus control: environmental affects on sleep, (c) sleep hygiene: planning for sleep, and (d) relaxation techniques to promote sleep. Attention control participants were given the “back health” control condition at study weeks 2 and 5, with data collection at baseline, three and five weeks, and two, three, and four months postbaseline.

• The sample included 30 participants.
• Mean age of participants was 53 years, with a range of 21–85 years.
• The sample was 63% female and 37% male.
• To be included in the study, participants had to be age 21 or older, be identified as a family caregiver living with a person with advanced cancer, and have reported difficulty initiating and/or maintaining sleep or nonrestorative sleep for at least one month, with no major diagnosis of depressive disorder or preexisting sleep disorder other than insomnia.
• The sample was 80% Caucasian, 10% African American, and 10% Hispanic.
• The relationships of the caregiver to the patient were spouse/partner (57%), adult children (30%), and other (13%).
• Hours of caregiving ranged from 2 to 24 hours, with an average of 17 hours.

• Single site
• Outpatient setting
• Central Texas

End-of-life care

A repeated measures experimental design was used.

• Pittsburgh Sleep Quality Index (PSQI) was used to measure caregivers’ sleep quality.  
• An actigraph sleep watch was used to measure sleep patterns (latency, duration, efficacy, and wake after sleep onset).
• Sleep Center for Epidemiological Studies–Depression Scale (CES-D) was used to measure current and immediate past symptoms of depressions.CES-D has demonstrated good reliability at α 0.85 in previous studies.
• Caregivers Quality of Life Index–Cancer (CQOLC) was used to measure caregiver quality of life. Contextual factors, including caregiver demographic characteristics, patient demographic characteristics, and sleep arrangements, were collected on a demographic sheet.
   

Feasibility: In terms of recruitment, caregivers were difficult to identify and recruit from the community setting but were enthusiastic once identified. In terms of retention, 35 recruited caregivers who met the inclusion criteria were consented and remained in the study through the final data collection.

CASI effectiveness: Sleep duration and efficiency were consistently strongly negatively correlated with caregiver depressive symptoms and quality of life over time. Overall sleep quality and sleep latency were consistently strongly positively correlated with caregiver depressive symptoms over time.

Caregivers’ quality-of-life scores showed improvement across groups. No significant differences or patterns of change were seen between or within groups. All study participants showed improvement in self-reported sleep quality during the study. Caregivers in the CASI intervention group reported greater improvement in overall sleep quality than did the attention control group caregivers at each time point  (CASI group: baseline, M 7.9 [3]; week 5, M 7.2 [3]; month 2, M 6 [3]; month 3, M 5.5 [3]; and month 4, M 5.4 [3]. Control group: baseline, M 7.9 [5]; week 5, M 7.6 [5]; month 2, M 8.4 [5]; month 3, M 7 [5]; and month 4, M 10.3 [6]). Significant differences were seen in caregiver self-reported sleep latency at week 5 (t = 2.29, p = 0.02) and in overall sleep quality then did attention control caregivers at month 4 (t = 2.40, p = 0.03).  

Actigraph data comparisons between groups showed significant differences in sleep latency scores at two months (t = - 2.57, p = 0.02) and duration scores at four months (t = 2.0, p = 0.05).

The CASI intervention group was significantly different from the control group in sleep latency at the end of four months. Sleep latency is defined as the amount of time it takes to fall asleep. Although this is only one aspect of sleep difficulties, it does show that CASI can be effective.

• The sample was small, with less than 100 participants.
• Risk of bias existed because there was no random assignment.
• The researchers had difficulty identifying subjects for recruitment from the community setting. 
• The sample had limited ethnic diversity.

Sleeping difficulty for caregivers of patients with advanced cancer who are not currently receiving hospice care is an important focus for nursing research because the area is understudied. One-to-one attention from a nurse and goal setting are powerful strategies that healthcare providers can use with family caregivers that can impact sleep improvements and reduction of depressive symptoms. The feasibility of a CASI intervention study is promising with some needed changes to the attention control group that were outlined in this study. The steady improvement in overall sleep quality of caregivers in the CASI intervention group demonstrated the possibilities of success in a future study.

The Yoga of Awareness Program included eight weekly, 120-minute, sessions, including gentle yoga postures, breathing exercises, meditation, didactic presentations, and group interchange. Patients were also encouraged to practice at home.

• The sample was comprised of 13 women with metastatic breast cancer.
• Mean age was 59 years (range 44–75).
• Eleven of 13 patients were Caucasian.

Duke Pain Prevention Program and Treatment Program Office

The study used an exploratory, pre-/post design; no control group was used.

• Brief daily diary using a visual analog scale (VAS) during two pre- weeks and the last two intervention weeks
• Focus group feedback

Those who withdrew had lower fatigue, which was interpreted as less motivation to participate. No significant change occurred in fatigue intercept (slope was not reported). There was a trend in which increased yoga practice was associated with decreased fatigue (p = 0.07). Lagged analysis showed that increased practice was predictive of decreased fatigue the next day. Participants reported that the program was successful to manage fatigue (mean = 7.6).

• The study lacked a control group.
• The study had a small sample size.
• Single-item daily measures were used.
• There was 28% attrition:  3 preintervention and 5 during the intervention.

No adverse events were reported. The intervention was led by a certified yoga instructor.

The study evaluated the effects of a yoga intervention on menopausal symptoms among breast cancer survivors.

Patients were randomized to the yoga intervention or a wait-list control group. The intervention consisted of eight weekly, 120-minute, group classes led by a certified yoga instructor. Classes were videotaped and reviewed. Sessions involved 40 minutes of stretching poses, 10 minutes of breathing techniques, 25 minutes of meditation, 20 minutes of study of pertinent topics, and 25 minutes of group discussion. CD recordings were provided for home practice. Application of concepts to daily life were assigned weekly. Assessments were performed at baseline, posttreatment, and three months postintervention. Wait-list controls were reminded about the assessments they needed. Patients kept daily diaries to rate hot flashes and daily use of yoga.

• The study was comprised of 37 women with a mean age of 54.4 years. 
• Patients were an average of 4.9 years since diagnosis.
• All patients had breast cancer, and 40.5% were stage IA.
• Of the patients, 70.3% had prior chemotherapy, 13.5% were on tamoxifen during the study, 75.7% were married or partnered, 81.1% were Caucasian, and 80.3% had college or graduate level education.
• Patients had no hormone therapy within three months.
• Many patients were on antidepressants.
• Of the patients, 50.5% were receiving aromatase inhibitors known to increase hot flashes.

The study was performed in outpatient clinics at Duke University.

• Patients were undergoing the late effects and survivorship phase of care.
• The study has clinical applicability for late effects and survivorship.

The study was a randomized, controlled trial.

• Patients kept daily hot flash and yoga use diaries. Hot flashes were scored on a 0-to-9 numeric scale.
• In addition, a questionnaire assessed the perceived credibility of the intervention.

Those in the yoga group had a significantly better decline in hot flash frequency, severity, joint pain, fatigue, and sleep disturbance (p < 0.002). Patients in the control group had significantly better decline in the degree to which they were bothered by symptoms (p < 0.0001). There was no difference in night sweats. Mean yoga practice time spent in use of techniques was associated with less fatigue (p = 0.032). Yoga daily participation ranged from 7.3 to 64.6 minutes. There was a 76% completion rate in the yoga group.

The findings suggested a potential benefit of a group yoga and support intervention for some symptoms in breast cancer survivors.

• The study had a small sample size.
• The study had no blinding or attentional control.
• It is unclear if the benefits were derived from the yoga activities or the group activities provided. 
• There was a relatively high drop-out rate, raising the question of the practicality of the intervention as designed. 
• The sample included patients with high education levels and current marriage or partnership support.
• Measurement of symptoms was not clearly described, and scoring was unclear.

The findings suggested that yoga and support activities provided in a group setting may help patients with symptoms of hot flashes, sleep deprivation, and fatigue. There was no apparent effect on night sweats.  

To examine the efficacy of two doses of venlafaxine:  37.5 mg (low-dose study) or 75 mg (high-dose study) to treat hot flashes after breast cancer.

Women were scheduled for 14 weekly visits. Weeks 1 and 2 provided baseline information, and weeks 3 to 14 included six weeks of treatment and six weeks of placebo.

Outcomes were hot flash (frequency, severity, and bother), hot flash impact on daily life, negative effect, fatigue, sleep, and quality of life (QOL).

The sample was comprised of breast cancer survivors:  57 in the low-dose study and 20 in the high-dose study.

University cancer clinics in the southeastern and midwestern United States

Patients were undergoing the long-term follow-up phase of care.

The study included two randomized, double-blind, placebo-controlled, crossover trials.

• Adherence was measured by capsule counts and weekly written verification.
• Sternal skin conductance monitor
• Electronic event markers and written diaries used for self-reporting hot flashes
• Profile of Mood States–Short Form (POMS-SF)
• Positive and Negative Affect Scale (PANAS)
• Center for Epidemiologic Studies Depression Scale (CESD)
• Diagnostic and Statistical Manual of Mental Disorders (DSM)
• Hamilton Rating Scale–Depression (HRSD)
• Pittsburgh Sleep Quality Index (PSQI) 
• Medical Outcomes Survey (MOS)

Venlafaxine resulted in modest decreases in hot flashes, but only hot flash interference improved differentially at the higher dose. The timing of the effect of venlafaxine on hot flashes varied by dose.

Only women with a 50% or greater decrease in physiologic hot flashes experienced significant improvement in fatigue, sleep quality, and QOL. Although side effects were mild, most patients discontinued venlafaxine long-term.

• The sample was racially and ethnically homogeneous.
• The study had a small sample size.
• Treatment time was limited.
• The study lacked pharmacogenetic data.
• In assessing hot flashes, subjective hot flash measures are prone to placebo effects, and subjective hot flash measures and secondary outcome measures may both be subject to a positive reporting bias.
• A study psychologist verified the absence of depressive symptoms, which could confound data if present.
• Trained study nurses are required.