Anxiety Disorders: Massachusetts General Hospital

Ongür D, Goff DC. · Schizophrenia Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. · Schizophr Res. · Pubmed #15885526 No free full text.

Abstract: OBJECTIVE: To determine the prevalence and clinical significance of obsessive-compulsive (OC) symptoms among a group of stable outpatients with schizophrenia. METHODS: We studied 118 patients with schizophrenia from an urban clinic, characterized using clinical symptoms scales, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and neuropsychological testing. We categorized patients into three groups according to severity of OC symptoms and used multivariate linear regression and chi-square tests to compare groups on variables of interest. RESULTS: Only 10 patients (8.8%) had Y-BOCS scores greater than 16, a standard criterion for OCD studies. The patient group with the most OC symptoms (Y-BOCS scores >11) scored higher on the Hamilton Depression Scale, the positive symptoms subscale of the Positive and Negative Syndromes Scale (PANSS) and its delusions item, but not on any of the neuropsychological tests compared to the other two groups. Patients with most severe compulsive symptoms (but not OC symptoms together, or obsessions alone) were more likely to be treated with olanzapine or clozapine, atypical antipsychotic medications previously reported to induce or worsen OC symptoms. CONCLUSIONS: Our results confirm previous findings that patients with schizophrenia and comorbid OC symptoms have more positive symptoms but not the suggestion that such patients are more cognitively impaired than their counterparts without OC symptoms. We suggest possible explanations for discrepancies in the literature, including differences in patient sampling and definition of comorbid OC symptoms. Finally, our data suggest that olanzapine and clozapine may produce or worsen compulsions in some patients; prospective studies need to address this possibility.

Otto MW, Deveney C. · Massachusetts General Hospital and Harvard Medical School, Boston, Mass, USA. · J Clin Psychiatry. · Pubmed #15842185 No free full text.

Abstract: In this article, we review the efficacy and applications of cognitive-behavioral therapy (CBT) for panic disorder. Research supports CBT as an effective first-line treatment of panic disorder that offers relatively quick onset of action and long-term maintenance of treatment benefits. These characteristics, plus the acceptability, tolerability, and cost-efficacy of CBT, make it an especially attractive treatment option for panic disorder. We review these findings as well as some newer developments in the field including research on emotional acceptance, the importance of context in extinction learning, and the use of CBT in combination with pharmacotherapy.

Simon NM, Fischmann D. · Massachusetts General Hospital, Harvard Medical School, Boston, Mass, USA. · J Clin Psychiatry. · Pubmed #15842182 No free full text.

Abstract: The frequent presentation of patients with panic disorder in medical settings may, in part, be explained by the physical symptoms inherent in panic disorder. However, a number of medical disorders have symptoms that overlap with panic disorder symptoms, and elevated panic disorder prevalence is comorbid with a number of medical illnesses, including respiratory disorders, vestibular dysfunction, and hyperthyroidism and hypothyroidism. The presence of medical comorbidity complicates the identification, presentation, and treatment of panic disorder. In addition, comorbid mood disorders occur commonly and result in greater severity, poorer quality of life, and greater impairment. Recent work suggests that panic disorder occurs more commonly with bipolar disorder than major depressive disorder, resulting in substantial impairment, as well as poorer response to treatment. The implications of mood disorder and its medical comorbidity for the identification and treatment of panic disorder are discussed.

Stevens JC, Pollack MH. · Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston, MA 02114, USA. · J Clin Psychiatry. · Pubmed #15762816 No free full text.

Abstract: Despite increasing focus on the use of antidepressants and other agents for the treatment of anxiety, benzodiazepines have remained a mainstay of anxiolytic pharmacotherapy due to their robust efficacy, rapid onset of therapeutic effect, and generally favorable side effect profile. In this article, we examine issues related to the long-term use of benzodiazepines, including concerns about the development of therapeutic tolerance, dose escalation, and adverse cognitive effects. We also consider currently available alternatives to benzodiazepines and novel mechanisms of action that may prove fruitful in the development of future generations of anxiolytics.

Stewart SA. · Massachusetts General Hospital, Boston, MA 02478, USA. · J Clin Psychiatry. · Pubmed #15762814 No free full text.

Abstract: Initially thought to be virtually free of negative effects, benzodiazepines are now known to carry risks of dependence, withdrawal, and negative side effects. Among the most controversial of these side effects are cognitive effects. Long-term treatment with benzodiazepines has been described as causing impairment in several cognitive domains, such as visuospatial ability, speed of processing, and verbal learning. Conversely, long-term benzodiazepine use has also been described as causing no chronic cognitive impairment, with any cognitive dysfunction in patients ascribed to sedation or inattention or considered temporary and associated with peak plasma levels. Complicating the issue are whether anxiety disorders themselves are associated with cognitive deficits and the extent to which patients are aware of their own cognitive problems. In an attempt to settle this debate, meta-analyses of peer-reviewed studies were conducted and found that cognitive dysfunction did in fact occur in patients treated long term with benzodiazepines, and although cognitive dysfunction improved after benzodiazepines were withdrawn, patients did not return to levels of functioning that matched benzodiazepine-free controls. Neuroimaging studies have found transient changes in the brain after benzodiazepine administration but no brain abnormalities in patients treated long term with benzodiazepines. Such findings suggest that patients should be advised of potential cognitive effects when treated long term with benzodiazepines, although they should also be informed that the impact of such effects may be insignificant in the daily functioning of most patients.

Wozniak J. · Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, MA 02138, USA. · J Clin Psychiatry. · Pubmed #15693748 No free full text.

Abstract: Bipolar disorder affects people of all ages, including preschool-aged children. Two major difficulties in diagnosing children with bipolar disorder are its overlap with attention-deficit/hyperactivity disorder (ADHD) and its developmentally distinct presentation from that in adults, with high rates of irritability, chronicity, and mixed states. Comorbid conditions are common in bipolar disorder and, in addition to ADHD, include depression, anxiety disorders, oppositional defiant disorder, and conduct disorder. Family studies have helped to confirm the validity of bipolar disorder in children. In terms of treatment, children do not appear to respond well to conventional mood stabilizers alone. However, using an atypical antipsychotic either alone or in addition to another mood stabilizer has shown utility in treating manic symptoms, depression in mixed states, and aggression. Amphetamine salts have been helpful in treating bipolar children with comorbid ADHD, but no data are available on treating comorbid depression in bipolar children. Because childhood-onset mania is commonly chronic rather than episodic, highly comorbid, and characterized by high rates of irritability, future clinical trials should examine the overlap of mania with other disorders in children to determine routes to accurate diagnosis and treatment.

Davis S. · Massachusetts General Hospital, Boston, USA. · J Assoc Nurses AIDS Care. · Pubmed #15587606 No free full text.

Abstract: Physical and mental changes resulting from HIV infection and its treatment can affect a patient's quality of life (QOL). Some of the most commonly reported symptoms affecting QOL in HIV-infected patients are fatigue, pain, anxiety/depression, and sleep disturbances. Fatigue often has a multifactorial etiology, including advanced HIV disease, opportunistic infections, poor nutrition, hormonal insufficiency, and anemia. Pain is one of the most overlooked factors by clinicians. Anxiety/depression and sleep disturbances are experienced by many HIV-infected individuals and are highly correlated with the perception and progression of disease. Although these common clinical symptoms impact QOL in HIV-positive patients, there are no established guidelines for treating them. As pain, anxiety/depression, and sleep disturbances can influence fatigue, as well as each other, the HIV care provider should monitor them closely because their severity reflects the clinical course of HIV as well as the overall well-being of the patient.

Otto MW, Perlman CA, Wernicke R, Reese HE, Bauer MS, Pollack MH. · Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Bipolar Disord. · Pubmed #15541062 No free full text.

Abstract: OBJECTIVES: In this article, we review the evidence for, and implications of, a high rate of comorbid posttraumatic stress disorder (PTSD) in individuals with bipolar disorder. METHODS: We reviewed studies providing comorbidity data on patients with bipolar disorder, and also examined the PTSD literature for risk factors and empirically supported treatment options for PTSD. RESULTS: Studies of bipolar patients have documented elevated rates of PTSD. Based on our review, representing 1214 bipolar patients, the mean prevalence of PTSD in bipolar patients is 16.0% (95% CI: 14-18%), a rate that is roughly double the lifetime prevalence for PTSD in the general population. Risk factors for PTSD that are also characteristic of bipolar samples include the presence of multiple axis I disorders, greater trauma exposure, elevated neuroticism and lower extraversion, and lower social support and socio-economic status. CONCLUSIONS: These findings are discussed in relation to the cost of PTSD symptoms to the course of bipolar disorder. Pharmacological and cognitive-behavioral treatment options are reviewed, with discussion of modifications to current cognitive-behavioral protocols for addressing PTSD in individuals at risk for mood episodes.

Fricchione G. · Division of Psychiatry and Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. · N Engl J Med. · Pubmed #15306669 No free full text.

This publication has no abstract.

Weilburg JB. · Massachusetts General Hospital, USA. · Manag Care. · Pubmed #15293768 No free full text.

Abstract: Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine re-uptake inhibitors (SNRIs) are used widely to treat mood and anxiety disorders. Indications, pharmacologic characteristics, and dosing and administration are outlined. Because more patients receive SSRIs in general medical versus psychiatric settings, this chapter includes information relevant to both.

Greenberg DB. · Department of Psychiatry, Massachusetts General Hospital, Boston, 02114, USA. · J Natl Cancer Inst Monogr. · Pubmed #15263054 No free full text.

Abstract: Major depressive disorder is a relapsing syndrome with grave morbidity and mortality. Much like asthma, it has a genetic predisposition and environmental triggers. Specific antidepressant medications alone, tested in randomized, placebo-controlled studies, show that this is a treatable condition with 65%-70% clinical response. Treatment guidelines written for psychiatric patients and patients in primary care clarify the role of medications and psychotherapy. Physicians are compelled to treat syndromes that are serious and treatable, but barriers to diagnosis and treatment of major depressive disorder in cancer patients include two major barriers to quality medical care generally: uncertainty and cost. Given uncertainty about diagnosis and treatment, cancer physicians with limited time avoid questions about emotions. Cases of depression are often missed. Mental health specialists often work in systems that are separated from oncologists by location, organization, and insurance. Most successful interventions to improve treatment of depressive disorders require multiple strategies: clinical education, enhanced role of nurses, and integrated oncology and specialist care. Recent strategies in oncology settings are reviewed. Research concepts to improve outcomes in treatment of depression include staging of depressive disorder in cancer to reveal prognosis, evaluation of depression outcomes in the context of one tumor type, new organizational models in the acute cancer setting, use of the cancer protocol, and assessment of access to care of depression in cancer survivors. Major depressive disorder in cancer is staged by positive past history, comorbid anxiety disorder or substance abuse, use of specific cancer medications that destabilize mood, and active cancer or no evidence of disease.

Cannistraro PA, Rauch SL. · Massachusetts General Hospital, Charlestown, MA 02129, USA. · Psychopharmacol Bull. · Pubmed #15131515 links to  free full text

Abstract: Present understanding of the neural circuitry of anxiety has come from a variety of sources, including animal, clinical, and most recently, neuroimaging studies. Evidence from these sources has converged to form a translational bridge from animal models to human pathophysiology. In particular, the classical fear conditioning paradigm has served as a foundation for this bridge. Proposed models for the neural circuitry of normal anxiety as well as the anxiety disorders are discussed. A brief review of specific findings from neuroimaging studies of posttraumatic stress disorder, specific phobia, social phobia, obsessive-compulsive disorder, and generalized anxiety disorder is also provided.

Brandes M, Soares CN, Cohen LS. · Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02114, USA. · Arch Womens Ment Health. · Pubmed #15083345 No free full text.

Abstract: The postpartum period is associated with an increased risk of developing obsessive-compulsive disorder (OCD) in women. Postpartum onset OCD is often undiagnosed and untreated resulting in serious consequences for the patient, her family and the newborn. The symptoms of postpartum onset OCD may consist of obsessional intrusive thoughts about harming the newborn without compulsions or with both obsessions and compulsions. In this review, the phenomenology of postpartum onset OCD is described as well as strategies for screening and diagnosis. The review also characterizes the differences between postpartum onset OCD and postpartum depression and postpartum psychosis and explores strategies for managing postpartum onset OCD patients. Issues regarding pharmacologic treatment of OCD in breastfeeding mothers are also reviewed.

Otto MW, Smits JA, Reese HE. · Massachusetts General Hospital and Harvard Medical School, Boston, Mass 02114, USA. · J Clin Psychiatry. · Pubmed #15078117 No free full text.

Abstract: In this article, we consider the evidence supporting the range of applications of cognitive-behavioral therapy (CBT) for anxiety disorders, and we examine some of the complex issues encountered for the combination of pharmacologic and cognitive-behavioral treatment strategies. The available evidence supports CBT as an effective first-line treatment for anxiety disorders offering longer-term maintenance of treatment gains. There is also evidence that CBT is an effective strategy for pharmacotherapy nonresponders, a replacement strategy for patients who wish to discontinue their medications, and a standard strategy for pharmacotherapy patients who need to boost their treatment response. Relative to combination therapy, we review some of the conditions that may influence the longevity of treatment gains from CBT.

Doyle A, Pollack MH. · Center for Anxiety and Traumatic Stress Related Disorders, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA. · J Clin Psychiatry. · Pubmed #15078115 No free full text.

Abstract: Panic disorder is a chronic, disabling condition that is often associated with a need for long-term clinical treatment. While a variety of pharmacotherapy options, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and benzodiazepines, are effective in reducing symptoms in the acute phase, a significant number of patients do not fully respond to initial treatment, and a large majority of patients experience relapse after medication discontinuation. Optimal long-term treatment of panic disorder involves attention to adequate medication dosing and adequate duration of treatment to achieve maximum improvement before discontinuing. Recent reports suggest the efficacy of adjunctive pharmacotherapies and combining pharmacotherapy with behavioral therapy to improve treatment response. Further research is necessary to determine the long-term effectiveness of these multifaceted treatment strategies among patients suffering from refractory panic disorder.

Rosenbaum JF. · Department of Psychiatry, Massachusetts General Hospital, Boston, USA. · J Clin Psychiatry. · Pubmed #15078111 No free full text.

Abstract: The pathophysiology of anxiety disorders is not clearly understood; therefore, clinical observation, case reports, and case reviews continue to enhance physicians' understanding of disease and treatment mechanisms. At Massachusetts General Hospital (MGH), physicians and researchers are guided by the recognition that available approved treatments are a small subset of what is sensible to try in anxiety disorders and have thus chosen to remain open minded and prepared to challenge assumptions about therapeutic agents and to explore new uses, including early work with high-potency benzodiazepines. Clinical trials established alprazolam as efficacious for panic disorder, and the agent was widely prescribed for patients at MGH after its approval. Soon, however, clinical observation suggested a short duration of benefit for a given dose in some patients. In some cases, patients who missed a dose reported rebound worsening. In response to the apparent problematic pharmacokinetics of alprazolam, members of the MGH psychiatry department pursued investigation that ultimately established the antipanic efficacy of clonazepam as well as examined its effectiveness in the treatment of other disorders, such as bipolar disorder and social phobia. The process of exploring new uses of older agents remains a worthy effort while we await newer agents with innovative mechanisms of action.

Shifren JL. · Menopause Program, Vincent Memorial Obstetrics and Gynecology Service, Massachusetts General Hospital and Harvard Medical School, Boston, Mass 02114, USA. · Mayo Clin Proc. · Pubmed #15065634 No free full text.

Abstract: There are many treatment options for female sexual dysfunction (FSD), with the optimal therapy depending on the etiology of the problem. The cause of sexual dysfunction is multifactorial and may include psychological problems such as depression or anxiety disorders, conflict within the relationship, partner performance and technique, issues relating to prior abuse, medical illness, medications, fatigue, stress, or gynecological problems that make sexual activity uncomfortable. The role of low androgen concentrations in FSD is gaining increasing attention. Available therapeutic options include adjusting medications, counseling, treating depression or anxiety, reducing stress and fatigue, sex therapy, devices, estrogen therapy for genitourinary atrophy, and possibly vasoactive substances. Although no androgen therapies are currently approved by the Food and Drug Administration for FSD, they are being used in clinical practice, and early clinical trial results suggest that they may be both effective and safe in the treatment of FSD, specifically low libido. Androgen therapy should be considered primarily in women who have a physiological reason for reduced androgen concentrations, including aging, hypopituitarism, oophorectomy, or adrenal insufficiency. Products in use include oral methyltestosterone and dehydroepiandrosterone, topical testosterone ointment, and testosterone implants and injections. Products available for men, including skin patches and gels, are currently being studied at doses appropriate for women. Possible risks include hirsutism, acne, liver dysfunction, lowering of the voice, adverse lipid changes, virilization of a female fetus, and, as androgens are aromatized to estrogens, potentially the risks of estrogen therapy.

Schwartz CE, Rauch SL. · Department of Psychiatry, Massachusetts General Hospital, and Harvard Medical School, Boston, 02129, USA. · CNS Spectr. · Pubmed #15048053 No free full text.

Abstract: We review the attributes of inhibited and uninhibited infant temperaments, and their developmental trajectories into early adulthood. Inborn individual differences in infants' propensity to respond to novel people and objects are associated with persistent differences in the responsivity of the amygdala to novelty, as measured with functional magnetic resonance imaging, after more than 20 years of development. Because an inhibited temperament is a risk factor for developing later psychiatric disorders, particularly generalized social anxiety disorder, temperamental differences are confounds in neuroimaging and genetic studies. Longitudinal studies are a unique tool for understanding the developmental and temperamental risk factors for psychiatric disorder.

Biederman J. · Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Department of Psychiatry, Harvard Medical School, Boston, USA. · J Clin Psychiatry. · Pubmed #15046528 No free full text.

Abstract: Persistence of attention-deficit/hyperactivity disorder (ADHD) into adulthood and male-to-female ratios of this disorder in childhood and adulthood have been controversial issues in the ADHD diagnosis in adults. Research has resolved these controversies and in turn provided support for the validity of the diagnosis in adults. Support for the diagnosis can also be found in data that show the lifetime prevalence rate for comorbid conditions such as antisocial disorders, mood and anxiety disorders, and substance abuse disorders to be consistent across pediatric and adult populations with ADHD. These coexisting conditions add not only to the impairment associated with ADHD in adults but also to the disorder's economic burden, the extent of which is currently unknown. However, adults with the disorder, like children, probably have higher health care use and costs than people without the disorder. Little, too, is known about the social cost of ADHD, but if left untreated, the impact may be substantial. Research to determine the occupational costs associated with ADHD is ongoing, but until that and other cost-of-illness data are available, studies on the economic costs of the comorbid conditions depression, anxiety, and substance abuse and dependence may be used to make suppositions about the economic impact of ADHD in adults. More studies are needed on the outcomes of adults with this disorder, especially cost-of-illness studies.

Papakostas GI, Ongür D, Iosifescu DV, Mischoulon D, Fava M. · Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, 15 Parkman Street, WACC #812, Boston, MA 02114, USA. · Eur Neuropsychopharmacol. · Pubmed #15013029 No free full text.

Abstract: Cholesterol plays an integral role in the structure and function of the cell membrane and may also affect neurotransmission in the central nervous system. Previous work has identified abnormalities in serum cholesterol levels in patients with mood and anxiety disorders as well as in suicidal patients. However, the biological significance of these abnormalities remains to be clarified. An understanding of how serum cholesterol relates to the pathophysiology of mood disorders may generate biological markers that predict treatment response as well as targets for novel therapeutic strategies. In this article, we review the literature studying the significance of cholesterol in mood and anxiety disorders, with an emphasis on new studies focusing on the adverse impact of hypercholesterolemia on the treatment of major depressive disorder (MDD). We then propose possible mechanisms that would account for the relationship between elevated cholesterol and treatment non-response in MDD.

Otto MW, Safren SA, Pollack MH. · Massachusetts General Hospital and Harvard Medical School, WACC-812, 15 Parkman St, Boston, MA 02114, USA. · J Anxiety Disord. · Pubmed #14725869 No free full text.

Abstract: Despite early recognition of the importance of internal cues (craving sensations and emotional states) for relapse in substance use disorders, relatively little attention has been devoted to exposure-based treatments targeting these cues. Drawing upon research on the conceptualization and treatment of panic disorder, we discuss the application of internal (largely emotional) cue exposure for substance use disorders. Our model for this discussion was based on the role of exposure to feared sensations of anxiety in the treatment of panic disorder and benzodiazepine (BZ) discontinuation. Shared research strategies between panic disorder and substance use--studies of biological provocation and anxiety sensitivity--were discussed, as were gender differences in drug-use motives. In accordance with research on anxiety sensitivity, provocation effects, and the treatment of benzodiazepine withdrawal, we discussed the potential value of internal cue-exposure strategies for individuals who use substances as a way to cope with negative affect.

Jenike MA. · Department of Psychiatry, Massachusetts General Hospital, Boston, USA. · N Engl J Med. · Pubmed #14724305 No free full text.

This publication has no abstract.

Doyle AC, Pollack MH. · Center for Anxiety and Traumatic Stress Related Disorders, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. · J Clin Psychiatry. · Pubmed #14658990 No free full text.

Abstract: Anxiety disorders such as generalized anxiety disorder, social anxiety disorder, panic disorder, and posttraumatic stress disorder are typically chronic conditions associated with high health care costs and are often accompanied by psychiatric comorbidity, including major depressive disorder, substance abuse, and other anxiety disorders. Anxiety disorders are associated with significant functional impairment in social, vocational, and familial spheres and with diminished overall quality of life. The following clinical overview provides informal guidelines for identifying remission in patients with an anxiety disorder. A systematic approach to treatment that includes patient education, encouragement of exposure, attention to relevant comorbidities, use of empirically proven pharmacotherapies, and psychosocial interventions of adequate intensity and duration will improve outcomes and move patients toward marked improvement and remission.

Pollack MH, Doyle AC. · Center for Anxiety and Traumatic Stress-Related Disorders, Massachusetts General Hospital, Boston, MA 02114, USA. · Psychopharmacol Bull. · Pubmed #14566201 links to  free full text

Abstract: Panic disorder is a chronic and disabling condition associated with significant morbidity. Treatment of panic disorder has evolved significantly in the past 20 years with the availability of serotonergic antidepressants, including the selective serotonin reuptake inhibitors (SSRIs). Of these, paroxetine was the first to receive an indication for treatment of panic disorder and has been extensively studied in this area. A series of randomized, double-blind, placebo-controlled studies have demonstrated the efficacy and safety of paroxetine treatment of panic disorder, with a majority of patients achieving panic-free status during 12-week studies. Continued treatment with paroxetine results in sustained rates of remission compared with placebo. The combination of paroxetine and cognitive behavioral therapy appears to offer benefits of efficacy and sustained therapeutic response.

Joffe H, Soares CN, Cohen LS. · Department of Psychiatry, Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, WACC, Boston, MA 02114, USA. · Psychiatr Clin North Am. · Pubmed #14563098 No free full text.

Abstract: More than 1 million women are expected to reach menopause each year, many of whom will experience hot flushes and other neuropsychological symptoms that may diminish their quality of life. Hot flushes are the core symptoms that reflect the brain's response to the changing hormonal milieu of the menopause transition, particularly to the rapidly fluctuating and falling levels of estradiol. The physical symptoms of hot flushes and the associated changes in sleep, mood, and cognition will lead many women to seek medical care. It is critical to understand the interrelationship of hot flushes and other neuropsychological symptoms of the menopause transition so that treatment priorities can be established. For example, if sleep disruption explains most daytime neuropsychological problems in women with hot flushes, treating insomnia should be considered a priority. Alternatively, mood, cognition, and quality of life may be disturbed independent of sleep problems. In such a situation, each symptom should be evaluated separately from any assessment of sleep. As recent data from the WHI establish the risks of long-term HRT use, concern about using HRT, even as a short-term intervention, has increased substantially. Although HRT remains the first-line treatment for hot flushes, the WHI findings have drawn attention to nonhormonal treatments of hot flushes and other menopausal symptoms. Growing evidence to support the efficacy of serotonergic antidepressants and other psychoactive medications in the treatment for hot flushes suggests that nonhormonal interventions will prove important alternatives to HRT. As further evidence of the benefits of psychoactive medications for menopausal symptoms is established, the choice between using hormonal and nonhormonal therapies for management of menopausal symptoms will continue to evolve.