Insomnia is a disorder characterized by chronic sleep disturbance associated with daytime disability or distress, such as memory impairment and fatigue, that occurs despite adequate opportunity for sleep. Insomnia may present as difficulty falling/staying asleep or as sleep that is nonrestorative. Studies show a strong correlation between insomnia and impaired quality of life. Pain conditions and depression are commonly associated with insomnia, either as secondary or comorbid conditions. In addition, a greater incidence of anxiety, alcohol and drug dependence, and cardiovascular disease is found in people with insomnia. Data indicate insomnia results from over-engaged arousal systems. Insomnia patients experience increased metabolic rate, body temperature, and heart rate, and elevated levels of norepinephrine and catecholamines. Pharmacologic options for the treatment of insomnia include benzodiazepine hypnotics, a selective melatonin receptor agonist, and sedating antidepressants. However, insomnia may be best treated with cognitive-behavioral therapy and instruction in good sleep hygiene, either alone or in concert with pharmacologic agents. Studies on the effects of insomnia treatment use variable methodologies or do not publish negative results, and there are currently no studies of treatment focusing on morbidity. Further research is necessary to better understand the effects of insomnia therapies on medical and psychiatric disorders.

In this Clinical Information Supplement, Thomas Roth, PhD, describes the nature of insomnia and its pathophysiology. Next, Andrew D. Krystal, MD, MS, reviews morbidities associated with insomnia. Finally, Joseph A. Lieberman III, MD, MPH, provides an overview of therapeutics utilized in patients with insomnia, including behavioral therapies and pharmacologic options.

Sleepiness is normal when it occurs toward the end of the day, at the beginning of the habitual sleep period. At this point, physiological sleep need has accumulated and the circadian rhythm no longer opposes sleep onset, facilitating the entry into sleep. However, when sleepiness occurs outside of the habitual sleep period it can become a medically significant problem.

The International Classification of Sleep Disorders, Second Edition (ICSD-2) defines excessive daytime sleepiness (EDS) as an inability to stay awake and alert during the major waking episodes of the day, resulting in unintended lapses into drowsiness or sleep. To differentiate this from the sporadic sleepiness that most people experience after a night or two of poor sleep, the ICSD-2 adds a frequency and duration criteria with most disorders requiring excessive sleepiness to be present daily or almost every day for at least 3 months (Slide 1).

A random sampling of patients taking a psychostimulant, an atypical antipsychotic, a combination of both, or neither were administered a brief examination to assess the possibility of abnormal motor movements induced by combining these classes of medications. Children on the combination demonstrated significant abnormalities when compared to those on either medication alone. This suggests a need for further study of neurologic risks associated with combining these medications.

How common is attention-deficit/hyperactivity disorder (ADHD), and does the prevalence change from adolescence to adulthood?

A number of studies have reviewed the persistence of attention-deficit/hyperactivity disorder (ADHD) from childhood into adolescence and adulthood as well as how the disorder changes over the lifespan of the illness. Recently, a metaanalysis found that the worldwide prevalence of childhood ADHD is ∼8%, and approximately two thirds of children with ADHD continue to have the disorder as adults. The National Comorbidity Survey is possibly the most comprehensive, up-to-date study examining the prevalence of community-based prevalence of adult ADHD; 4.4% of patients in that study were found to have ADHD. The prevalence of ADHD among adolescent patients seems to lie somewhere between the prevalence rates for children and adults.

A PubMed search revealed 14 cases of ziprasidone associated mania, which carried primary diagnoses of mood disorders, generalized anxiety disorders (GAD), panic disorder, and psychotic disorders. To our knowledge, we report the first case of mania associated with ziprasidone augmentation of a selective serotonin reuptake inhibitor in a 60-year-old man (at time of ziprasidone-induced mania) with obssessive-compulsive disorder (OCD).

In May 2002, after partial response to citalopram 80 mg and low-dose clonazepam 1.5 mg/day in three divided doses, ziprasidone was initiated as an augmenting agent at a dose of 20 mg/day and increased to 20 mg BID. Within 7 days of starting ziprasidone family members noted a decreased need for sleep, impulsivity, grandiosity, and increased energy. He was brought to the emergency room after 17 days with florid manic symptoms. Physical and neurological exams were unremarkable. Routine laboratory work, including a drug screen, was non-contributory. His non-psychiatric medications included fexofenadine, hydroxyzine, and sodium nitroprusside. He was hospitalized and ziprasidone was stopped with reduction in the dose of citalopram to 20 mg. Manic symptoms promptly resolved within 3 days.

The syndrome now known as involuntary emotional expression disorder (IEED) is a condition characterized by uncontrollable episodes of laughing and/or crying. It has been known for more than a century, but confusing and conflicting terminology may have hampered the progress of physicians in recognizing this condition. IEED is associated with various neurological disorders and neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, and neurological injuries such as stroke and traumatic brain injury. It is hoped that better defined terminology for IEED may help in the future diagnosis of this debilitating condition, the establishment of accurate prevalence rates for IEED in the varying underlying conditions, and also in removing blame and stigma from sufferers by providing reassurance about the nature of their condition.

In awareness of recent developments and upcoming future changes in the conceptualization of obsessive-compulsive disorders (OCDs), a group of 14 experts with specific experience in this area decided that a consensus statement on the present and future of OCD is timely. The group, with their long-term interest and productivity in the area of OCD, met with the specific aim of providing a global perspective.Ten countries from four continents were represented in this 2-day consensus meeting.

The meeting took place in Cape Town on February 27–28, 2006. The participants were asked to prepare and submit a relevant presentation before the meeting in order to enrich the discussion. Six presentations reviewed the following aspects of OCD: diagnosis, epidemiology, neurobiology, treatment, special populations, and pediatric OCD. A draft consensus was prepared, based on the presentations, recent consensus statements, evidence-based guidelines, and the ensuing discussions. On the second day the consensus was subjected to review and comments from all the participants. Further work progressed via E-mail and a subsequent follow-up meeting in Toronto in May 2006. The enclosed supplement represents the outcome of this joint effort.

Although obsessive-compulsive disorder (OCD) is classified as an anxiety disorder in the DSM-IV, recent considerations for a reclassification into an obsessive-compulsive spectrum disorders (OCSDs) cluster are gaining prominence. Similarities in symptomatology, course of illness, patient population, and neurocircuitry of OCD and OCSD are supported by comorbidity, family, and neurological studies, which also offer a critical re-evaluation of the relationship between OCD and anxiety disorders. This review examines potential classifications of OCD among the wider spectrum of affective disorders and at the interface between affective disorders and addiction. In addition, it has been suggested that the categorical diagnostic approach would be enhanced by an additional dimensional approach, including parameters such as stability of mood and ability to sustain attention. With further studies, it is ultimately the goal to define OCD and related disorders based on endophenotypes.

Despite efforts in this field, there are several fundamental unresolved issues, including the question of which disorders should be grouped together in this category and which characteristics to include as their shared common features. A reclassification of OCD among the OCSDs would allow for better scrutiny of distinct obsessive-compulsive symptoms, as currently this disorder often goes undetected in patients who complain of a broad symptom of anxiety. Advantages and disadvantages of establishing OCSDs and its implications for diagnosis, treatment, and research are discussed.

Until recently, depression was considered an acute, self-remitting illness of limited duration. However, it is increasingly recognized as a chronic, relapsing, or recurrent illness in most patients, imposing a substantial burden on the individual and society. Research has demonstrated an association between depression and impaired psychosocial functioning, reduced productivity and life satisfaction, excess health care utilization, increased reporting of medically unexplained medical symptoms, comorbidity with other psychiatric illnesses, and suicide. It is more prevalent in patients with common chronic medical conditions, such as obstructive pulmonary disease, hypertension, diabetes, stroke, coronary artery disease, asthma, and chronic pain. In addition to its association with medical morbidity and mortality, depression has a negative impact on self-care behaviors, including medication adherence, in patients with chronic medical illnesses, and in health-related behaviors such as exercise, smoking, and weight control. As a consequence, it is a major barrier to effective care of chronic medical illnesses.

One of the most challenging clinical topics in psychiatry is the diagnosis and treatment of bipolar depression. The term mood stabilizer is frequently employed in the treatment of the hospitalized bipolar patient, although clinicians do not universally agree on a consensus definition of this term. Most clinicians would agree that a mood stabilizer refers to a medication that is effective for the acute treatment of manic, mixed, hypomanic, or depressive episodes. Many experts agree that such treatment should offer efficacy against mania, should not worsen depression, and preferably should treat depression as well. In addition, the acute effectiveness in stabilization should not be at the expense of inducing alternate mood symptoms or switching the patient into the alternate phase of illness. From a maintenance standpoint, a mood stabilizer should also prevent against future relapse or recurrence of manic, mixed, hypomanic, or depressive symptoms or episodes (Slide 1).

In addition to use of mood stabilizers, there are other issues surrounding treatment of the hospitalized patient with bipolar depression, including the commonly comorbid issue of substance abuse. Hazardous drinking may more commonly occur in bipolar depression or depressive phase of illness, representing a more complex clinical picture. To facilitate understanding of this complex disorder and its appropriate treatment, this discussion centers around the case of a major depressive episode in a patient with a past history of of mania (ie, bipolar I depression or bipolar depression).

Clinicians are fairly comfortable with the management of acute mania because of the abundance of research studies available. However, there are several important aspects of bipolar disorder that the field has been far less successful with, including management of acute and preventive treatment of bipolar depression, comorbid illnesses, and break-through depression in the context of long-term treatment. There is tremendous complexity in the various symptoms and behavioral dimensions associated with bipolar depression. To facilitate understanding of bipolar depression, this article focuses on treating and managing the bipolar outpatient at risk for a depressive relapse. The discussion poses several challenges associated with bipolar depression and addresses the morbidity of depressive states as well as acute and long-term management of this disorder. The best practices for the varying clinical states of bipolar depressive disorder will be demonstrated through two case examples of patients struggling with disturbances common in bipolar patients.

Attention-deficit/hyperactivity disorder (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present to primary care physicians, psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiologic basis, complex etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric comorbidity is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds) have shown robust efficacy and tolerability consistent with the treatment response established in children with ADHD. Non-stimulant medications have demonstrated efficacy as well, and may be preferred in patients with tic and substance use disorders.

In this expert roundtable supplement, Timothy E. Wilens, MD, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MD, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MD, reviews stimulant treatment of adult ADHD, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adult ADHD.

Pharmacoepidemiology, the study of the effects of drugs in large numbers of people, is a relatively new discipline that applies the methods of epidemiology to clinical pharmacology. Premarketing clinical trials remain the only way to scientifically determine whether a drug is causally effective, yet these trials do not provide information that allows for estimates about rare, late, or off-label toxicities associated with the drug in question. Increasing concern about common and debilitating adverse effects of medications has highlighted the need for enhanced postmarketing surveillance to follow up on clinical trials. There is a further concern regarding the broader issue of the risk-benefit ratio of certain medications. Computerized databases are a good source of information on which to lay the foundations of postmarketing research. A system of cross-linked computerized medical records may better enable researchers and physicians to realistically monitor postmarketing safety and incorporate monitoring benefits. The same research could also elucidate the net public health effect of regulatory decisions. The Veterans Affairs database in the United States and PHARMO in the Netherlands may represent good models on which to base future postmarketing surveillance studies.

In this expert roundtable supplement, Brian L. Strom, MD, provides an overview of the appropriate use of large computer databases in pharmacoepidemiology studies. Philip Wang, MD, DrPH, discusses the advantages of pharmacoepidemiologic studies over clinical trials in correctly detecting drug safety issues. Francesca Cunningham, PharmD, reviews a large computer database that is currently in use within the VA healthcare system, and Ron M.C. Herings, PharmD, PhD, discusses the development of the PHARMO system in the Netherlands.

This summary is based heavily on the concepts presented in: Strom BL. What is pharmacoepidemiology. In: Strom BL, ed. Pharmacoepidemiology. 4th ed. Sussex: John Wiley; 2005:3–15; and Strom BL. Overview of study designs available for pharmacoepidemiology studies. In: Strom BL, ed. Pharmacoepidemiology. 4th ed. Sussex: John Wiley, 2005:17–28.

Augmentation strategies have become popular in patients with a partial response or residual symptoms. In a survey conducted by the American Society of Consultant Pharmacists, 65% of 169 psychiatrists indicated that they would augment treatment as the next step in a partial responder in contrast to non-responders in whom they would switch to another drug (J.C. Nelson, unpublished data). This decision is based on common sense and practicality rather than empirical evidence. Many clinicians and patients think that if a patient achieves at least a partial response to a medication, it makes sense to continue that drug and add a second. To some extent, the patient preferences for treatment shown in the Systematic Treatment Alternatives to Relieve Depression (STAR*D) study reflect this approach. This discussion will update clinicians on the use of augmentation agents for the treatment of major depressive disorder (MDD).

Lithium augmentation has been used since it was first described by de Montigny and colleagues in 1981. This strategy is based on a rational neurochemical hypothesis that lithium has a synergistic effect when added to a tricyclic antidepressant (TCA). Lithium increases serotonin turnover and the TCA increases postsynaptic serotonin receptor sensitivity. Recent debates have focused on whether lithium is as effective combined with selective serotonin reuptake inhibitors (SSRIs) as it is combined with a TCA. The rapid effects sometimes observed with lithium augmentation of TCAs does not seem to occur with SSRIs, conceivably because SSRIs do not increase postsynaptic serotonin receptor sensitivity.

Recognizing drug-drug interactions (DDIs) has become increasingly important as the country's demographics have aged, resulting in more complex medication regimens. Budnitz and colleagues highlighted the frequency of adverse drug reactions (ADRs) and the substantial morbidity that results. Their study estimated >700,000 cases of ADRs in emergency rooms (ER) in the United States between 2004 and 2005, and that ADRs accounted for 6.7% of ER visits for unintentional injuries that led to hospitalization. Moreover, medications that require monitoring accounted for 41.5% of all the ADR-related hospitalizations.

These data have tremendous implications for the field of psychiatry because many psychiatric drugs require therapeutic monitoring. The importance of DDIs is particularly relevant for the psychiatric population, where adverse effects not only cause short-term morbidity, but may lead to long-term treatment noncompliance. For many patients taking antipsychotics, adherence is the key to a successful outcome. Minimizing DDIs maximizes the chance that people will avoid unnecessary ADRs while achieving therapeutic drug levels.