The last 4 years have seen a rapid burst of development of medications used to treat epileptic seizures. While none of these medications has replaced the “standards” in the field, they collectively offer additional treatment options for patients, particularly for those with difficult-to-control seizures. As experience with these novel medications grows, each will occupy its own niche in the treatment strategy for patients with epilepsy.

There are many new findings in the area of comorbid insomnia. Almost 50% of all cases of chronic insomnia are due to a mental disorder, with depressive illness explaining the majority of cases related to mental disorder (Slide 1). Other common causes of comorbid, or secondary, insomnia include chronic respiratory disease such as asthma and chronic obstructive pulmonary disease, chronic pain, degenerative neurological disease, and some medications such as glucocorticoids and serotonin reuptake inhibitors. A general principle of management of insomnia related to mental or medical disorders is that the principal disorder must be fully treated as part of the insomnia treatment plan. If there is an offending medication, it must be discontinued if possible.

In discussions of diversion and misuse of medications in adult attention-deficit/hyperactivity disorder (ADHD), the word “misuse” is intentionally used. Abuse of a medication refers to excessive use of a drug to achieve a “high,” which may result in addiction to the medication and which causes dysfunction in a patient's life. However, misuse refers to usage of a medication without a prescription or for reasons other than that which it was prescribed. Diversion refers to the diverting of legally prescribed medication into illegal use by other than the patient. Sahakian and Morein-Zamir recently discussed the use of cognitive-enhancing drugs by individuals with a variety of disorders as well as off-label and non-prescription use by the general public. In addition to inappropriate use of medications, patients with ADHD often turn to other substances that are detrimental to their health, such as nicotine.

While the public health perspective prioritizes large populations of affected individuals, our job as clinicians is to help one patient at a time. Over the last 10–20 years, there has been marked improvement in pharmacologic and psychosocial interventions available for patients with anxiety disorders (Slide 8).

The use of antidepressants, particularly the serotonergic and serotonergic noradrenergic agents, have received increased attention as first-line treatment for most of the anxiety disorders, including panic disorder, social phobia, posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Antidepressants are often used as first-line therapy for anxiety disorders because of their broad spectrum of efficacy against common comorbidities, especially depression, and because of concern about benzodiazepine-associated dependence, abuse liability, and lack of efficacy for depression and other comorbidities (Slide 9).

These newer antidepressants have advantages over the older antidepressants, particularly the tricyclics and the monoamine oxidase inhibitors, in that they are generally better tolerated and more appropriate for use in potentially suicidal patients because they are less lethal in overdose. However, there are some side effects that may limit their use in some patients. In the case of the serotonergic antidepressants, many patients are hesitant to initiate or maintain treatment due to concerns about sexual dysfunction.

The 12-month and lifetime prevalences of bipolar I and II disorder in the United States are 2.0% and 3.3%, respectively. Similar to schizophrenia, bipolar disorder is also associated with premature and excess mortality, with an estimated loss of ∼15 years of life expectancy. Most of the excess mortality in individuals with mood disorders results from natural causes, not suicide. Again, similar to schizophrenia, the most common cause of death in patients with bipolar disorder is cardiovascular disease (CVD), which occurs approximately twice as often in this group as in the general population. Although the data are more limited than in schizophrenia, people with bipolar disorder are differentially affected by medical comorbidity. Bipolar disorder is associated with elevated risk of a wide variety of comorbid medical illnesses, including migraine, asthma, chronic bronchitis, hypertension, and gastric ulcer, which compound disability and increase the burden of the disease.

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.

Are reproductive life events in women associated with an increased risk of sexual dysfunction? Female sexual dysfunction effects up to 40% of women in the United States between 18 and 59 years of age. Sexual dysfunction may be accompanied by fluctuations in gonadal hormone secretion, making women more vulnerable to sexual symptoms, especially during times of reproductive life events. Reproductive life events, such as the use of birth control pills, various phases of the menstrual cycles, postpartum and lactation states, and perimenopause, are highly correlated with changes in sex steroids. As an understanding of the role of sex steroids on sexual functioning is elucidated, clinicians will be able to offer more specific and effective treatment options for women during various phases of reproductive life. Several case studies are presented to illustrate the unique clinical considerations that a clinician must consider when treating the biologic component of female sexual dysfunction.

Psychoneuroendocrinology (PNE) has been a method used in the past to investigate brain biochemical functions in normal and pathological mentation. These studies have subsequently uncovered variations in normal biochemical functioning. It is still being debated, however, how these variations correlate with well-defined psychopathologies.

Future studies in PNE shows promise in many areas of contemporary neurospychiatry. For example, research focusing on variations in neurotransmitter, neuropeptide, and neurohormone secretory tonus might enhance our understanding of specific personality characteristics and behavior. PNE may also be essential in investigating the correlation between hormonal variations and symptoms observed across various psychiatric disorders. PNE might likewise be important for new therapeutic approaches. Finally, PNE can be used to investigate psychoneuroimmunoendocrine relationships.

New PNE methodologies must be developed to make this branch of neuroscience more appropriate for the study of localized brain functions.

Although most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity.

In this monograph, David A. Mrazek, MD, provides an overview of the context of genetic testing in clinical psychiatric practice. Next, Jordan W. Smoller, MD, ScD, discusses some of the practical issues related to medication selection. Finally, Jose de Leon, MD, presents a comprehensive review of antidepressant and antipsychotic treatment based on drug metabolism, and reviews the available testing methods for CYP 2D6 and 2C19 genotypes.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The last 5 years have been marked by rapid developments in understanding the pathophysiology of PD as well as by the introduction of a number of new drugs for symptomatic treatment of the disease. On the other hand, the diagnosis of PD is still made purely on clinical grounds. Due to continuing advances in therapy, it is increasingly important to recognize PD in its earliest stages and to distinguish it from other causes of parkinsonism, for which prognosis and response to treatment differ. This article reviews the epidemiology of PD and then elaborates on the diagnosis and differential diagnosis.