What exactly is known today about the impact of the adult form of attention-deficit/hyperactivity disorder (ADHD) in society?:

In a recent study to examine the societal impact of attention-deficit/hyperactivity disorder (ADHD), 500 patients diagnosed with ADHD and 501 participants with no substantial signs or symptoms of ADHD were studied. Subjects were asked several questions about their quality of life, employment, job satisfaction, and other aspects of their well-being and functionality. Income, which is an important marker for the degree of productivity for an individual in society, was also assessed. ADHD can profoundly affect the performance of individuals in the workplace (Slide 1), and this study found that having ADHD reduced an individual's income by an average of ∼$10,000 per year. If that loss of income is extrapolated to all adults in the United States who have ADHD, it suggests that the economy is losing around $70 billion a year to $115 billion a year in productivity, as measured by loss of income. The range was broad because different models with varying assumptions were applied to project income loss over time. Nevertheless, based on these numbers, it is reasonable to estimate that the population is losing ∼$100 billion annually in productivity due to ADHD.

Income loss was found at all levels of education, but it was greatest among patients who had advanced degrees of education; so it seems that the disease may have a more pronounced impact on income among those in the higher income brackets.

Antidepressants have been available since the 1950s, when the monoamine oxidase inhibitors were first discovered. Since then, our armamentarium of antidepressants has progressively expanded with the discovery of the tricyclic antidepressants (TCAs) in the 1960s, the selective serotonin reuptake inhibitors (SSRIs) in the 1980s, and, subsequently, the serotonin norepinephrine reuptake inhibitors (SNRIs), and other agents possessing a diverse mechanism of action including buproprion, and mirtazapine.

Underdiagnosis and undertreatment of late-life depression is common, especially in primary care settings. To help assess whether physicians' attitude and confidence in diagnosing and managing depression serve as barriers to care, a total of 176 physicians employed in 18 primary care groups were administered surveys to assess attitudes towards diagnosis, treatment, and management of depression in elderly patients, (individuals over 65 years of age). Logistic regression was performed to assess the association of physician characteristics on attitudes. Nearly all of the physicians surveyed felt that depression in the elderly was a primary care problem, and 41% reported late-life depression as the most common problem seen in older patients. Physicians were confident in their ability to diagnose and manage depression, yet 45% had no medical education on depression in the previous three years. Physicians' confidence in their ability to diagnose, treat, and manage depression, and their reported adequacy of training, do not appear to correspond to the amount of continuing medical education in depression, suggesting that physician overconfidence may potentially be serving as a barrier to care.

Panic disorder seems to be mediated by the neuronal circuitry and neurochemical systems that have evolved to respond to external threatening stimuli. Distant threats activate prefrontal cortex (involved in complex planning of avoidance strategies), while immediate threats activate midbrain structures (involved in fast reflexive behaviors). Panic disorder may, however, also involve more specific interoceptive mechanisms. For example, the association between respiratory dysfunction and panic disorder has bolstered a false suffocation alarm hypothesis. Genetic and environmental contributors to panic disorder are beginning to be delineated. Effective pharmacotherapy and psychotherapy are able to normalize the relevant psychobiology.

What is the current knowledge concerning the pharmacologic treatment of human sexual dysfunction? A number of interventions, including oral phophodiesterase inhibitors and intracorporeal agents with vasodilatory effects, are available to treat male erectile disorder. Serotonergic drugs have been shown to be effective in the treatment of rapid ejaculation. Various lines of research suggest that high dosages of androgenic agents may eventually have a role in the treatment of decreased libido in females. There may be a role for phophodiesterase inhibitors in the treatment of a subgroup of women with arousal disorders. Normal sexual function involves successful integration of biological, psychological, and interpersonal influences. Clinical psychiatry with its biopsychosocial model should incorporate the treatment of human sexual dysfunction within its purview.

This short-term, open-label study investigates short- and long-term effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine for the treatment of trichotillomania (TTM). Additionally, this study aimed to test the hypothesis that the presence of hair pulling compulsiveness is predictive of SSRI response. Nineteen subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, (DSM-III-R) criteria for TTM were treated with fluvoxamine at doses up to 300 mg/day. Random regression analysis of change across time for patients who completed the study (n=14) and those who dropped out (n=5) revealed statistically significant improvements in Physician Rating Scale, hair-pulling episodes, Trichotillomania Impairment Scale, and Trichotillomania Symptom Severity Scale, but not in estimated amount of hair pulled. In addition, the percentage of patients' focused or compulsive hair-pulling symptoms was predictive of treatment response. Unfortunately, all three subjects who entered long-term treatment displayed substantial movement back toward baseline by the end of 6 months. We concluded that fluvoxamine produces moderate reductions in symptoms during the short-term treatment of TTM and that the presence of focused or compulsive hair pulling may be predictive of treatment response. However, responses may be short lived when treatment is extended.

Pharmacogenetics brought the promise of matching individuals with treatments that would be efficacious while minimizing adverse events. This has been long needed in psychiatry, where treatment options have been empirical and treatment choices have been made largely based on clinical judgment. The efficacy and tolerability of antidepressants, the most common drugs used in mood disorders, have been widely studied in pharmacogenetics. Genetic association studies have been reported for pharmacokinetic genes such as the CYP450 isoenzymes or MDR1, and pharmacodynamic genes such as the serotonin transporter (SLC6A4) or the serotonin 2A receptor (HTR2A). However, despite the large number of reports, clinically useful predictors are still scarce for antidepressant monotherapy. Pharmacogenetic predictors of efficacy for mood stabilizers such as lithium and anticonvulsants have not had a dissimilar fate, and clinically meaningful markers are yet to emerge. The lack of consistent results may be in part due to small samples of heterogeneous populations and lack of consensus on phenotype definitions. Current pharmacogenetic recommendations include testing for HLA-B*1502 when using carbamazepine in Asian ancestry populations to prevent Stevens–Johnson syndrome, CYP2D6 genotypes when using pimozide, and CYP2D6 in polypharmacy to minimize drug interactions. This review, which is aimed at clinicians, lays the basis for understanding strengths and weaknesses of pharmacogenetic studies and outlines current clinical uses of these biomarkers.

In September 2005, the National Institute of Mental Health published phase 1 results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, a large-scale, double-blind trial comparing the relative effectiveness of five antipsychotics used to treat patients with schizophrenia: perphenazine, a conventional antipsychotic that has been commercially available since the 1950s, and four atypical agents—olanzapine, quetiapine, risperidone, and ziprasidone—that were introduced in the 1990s. The broad intention of the CATIE study is to determine if the atypical agents used offer any demonstrable clinical and public health advantages over the conventional agents. Concerns over costs and side effects (eg, pronounced weight gain and lipid disturbances) associated with the newer, atypical antipsychotics, as well as doubts about superior efficacy relative to older, conventional agents, served as an impetus to the trial.

The study design chosen for the CATIE study—that of a “large, simple” trial—sought to bypass the limitations of clinical studies that are conducted when pharmaceutical companies seek regulatory approval of a new medication. Studies done in pursuance of drug approval attempt to establish safety and efficacy in controlled clinical settings so as to determine if a drug works at all, and if its use entails specific side effects. Hence, they are typically placebo-controlled and short-term, enroll a small homogeneous population (eg, initially hospitalized patients with no psychiatric or medical comorbidities), forbid or restrict the use of concomitant medications, and take as their endpoints well-defined side effects and measures of core psychopathology. These restrictions heighten the risk that the study findings may not be widely applicable to patients outside the confines of the protocol.

Diffusion tensor magnetic resonance imaging is an imaging modality that measures the diffusion properties of water molecules in tissues noninvasively. Water diffusion is affected by tissue constituents, such as macromolecules, membranes, organelles, as well as by tissue microstructure, architecture, and organization. From the quantities measured with diffusion tensor-magnetic resonance imaging, one can infer information about brain tissue that cannot be obtained using conventional, compositional-based (eg, proton density and chemical spectroscopy), or relaxometry-based (eg, magnetization transfer, T1, T2, and T2*) magnetic resonance imaging methods. Understanding the relationship between a measured water diffusion pattern and the underlying histological features of the tissue, however, is not simple. In the absence of a robust and comprehensive model of water diffusivity in biological tissues, the biological interpretation of diffusion measurements relies on empirical evidence. Herein, the properties of several diffusion tensor-derived quantities are reviewed, together with the experimental evidence that helps clarify their relationship with the underlying properties of brain tissue.

Pharmacogenomic testing can be integrated into modern mental health practices to help select psychotropic drugs for individuals who have failed first-line evidence-based treatments. This can be done by the process of “equipoise”—namely, balancing the weight of all available evidence. That evidence now includes not only diagnosis-specific treatment guidelines and “personalized” patient information, such as an individual’s specific symptom profile, past response to medications, side effects, family history, and patient preference, but also “precision medicine,” which incorporates the ever-expanding base of pharmacogenomic evidence for how an individual’s own biomarkers alter the odds for that individual’s treatment response or treatment intolerance.

Patients with Parkinson’s disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions. A panel of experts drew from published data, their experience treating PDP, lessons from switching antipsychotic drugs in other populations, and the pharmacology of the relevant drugs, to establish consensus recommendations. The panel concluded that patients with PDP can be safely and effectively switched from atypical antipsychotics used off label in PDP to the recently approved pimavanserin by considering each agent’s pharmacokinetics and pharmacodynamics, receptor interactions, and the clinical reason for switching (efficacy or adverse events). Final recommendations are that such a switch should aim to maintain adequate 5-HT2A antagonism during the switch, thus providing a stable transition so that efficacy is maintained. Specifically, the consensus recommendation is to add pimavanserin at the full recommended daily dose (34 mg) for 2–6 weeks in most patients before beginning to taper and discontinue quetiapine or clozapine over several days to weeks. Further details are provided for this recommendation, as well as for special clinical circumstances where switching may need to proceed more rapidly.

The materials in the following section are speaker comments from an educational symposium entitled Suicide: Clinical/Risk Management Issues for Psychiatrists sponsored by the American Psychiatric Association, May 16, 1999. The program chairpersons were Drs. Douglas Jacobs and Ross J. Baldessarini. The symposium was supported by an unrestricted educational grant from Solvay Pharmaceuticals.

The symposium focused on critical clinical and risk management issues about suicide as they impact clinical practice. Dr. Douglas G. Jacobs presented a suicide assessment protocol with suggestions on how to include current understanding about suicide in treatment planning. Dr. Kay Redfield Jamison reviewed bipolar disorder with an emphasis on early diagnosis, aggressive treatment, and the phenomenology of suicidal behavior. Dr. Ross J. Baldessarini discussed the lethality of bipolar depression and the effectiveness of lithium maintenance therapy to limit bipolar depression and reduce suicide risk. Dr. Jan A. Fawcett presented four clinical profiles of completed suicide and reviewed suggested treatment approaches appropriate for each that may help psychiatrists reduce the risk of suicide among their patients. Dr. Herbert Hendin explored the role psychiatrists play in performing comprehensive assessments of patients who request assisted suicide. Finally, Dr. Thomas G. Gutheil reviewed the basis for malpractice litigation and provided guidelines for preventing liability following a patient's suicide.

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.