The diagnosis for posttraumatic stress disorder (PTSD) requires that onset be initiated by a negative life event. The event is considered capable of producing PTSD if it creates a threat to the person's physical integrity and produces a reaction of shock and horror. The traumatic events most frequently described in the research literature are combat and rape. These events are well known to produce the three symptom clusters that comprise PTSD and include: (A) re-experiencing symptoms, such as nightmares, sudden unbidden intrusive images and thoughts of the event, and flashbacks; (B) symptoms classified as avoidance, including efforts to avoid thoughts and feelings related to the event, sense of foreshortened future, and emotional numbing; and (C) symptoms of hyperarousal, such as hypervigilance and exaggerated startle response.

The nature of PTSD, particularly that it emerges from significantly disturbing life experiences, may contribute to the limited inquiry about the presence of the disorder among youths. It is difficult to consider that children and teenagers are exposed to terrible events such as physical assault, rape, and mass violence, which frequently lead to sustained psychiatric problems. However, the reality is that children and adolescents experience more violence than adults and that PTSD appears among youth at a rate equivalent to that of adults.

Parkinson's disease is a progressive neurodegenerative disorder with prominent motor features. The cardinal motor signs, bradykinesia, rigidity, and tremor, are treated effectively by dopaminergic therapies. Levodopa is standard, and often initial, therapy for patients with this condition. However, with continued treatment, and as the disease progresses, the response to oral dopaminergic drugs becomes unstable and motor fluctuations emerge, including off periods (when medication effects wear off) and dyskinesia (dystonic or choreatic movements) (Slide 1). Risk factors for motor complications include younger age at disease onset, longer disease duration, higher levodopa dosage, and more severe motor symptoms.

For decades following the 1906 identification of Alzheimer’s disease (AD), it was believed that the disorder was untreatable. Only in the late 1970s, with the introduction of the cholinergic hypothesis of the underlying mechanisms of AD, were treatment options considered possible. The first positive treatment study was conducted in 1985. In 1993, tacrine, a cholinesterase inhibitor, was approved for the treatment of AD; three similar drugs soon followed. Memantine, an NMDA receptor antagonist, was approved in 2003, representing a second therapeutic class for AD.

Cholinesterase inhibitors were the first therapeutic options successfully employed, and there is strong evidence these agents confer benefits. The addition of memantine to the standard course of therapy can be beneficial as well, particularly at the moderate stages of the disorder (Mini-Mental State Exam score of ≤14). For patients without cardiovascular disease, diabetes, or statin use, 1,000 IU vitamin E BID is a consideration to mitigate the effects of AD. However, there is presently concern over the risks involved in vitamin E therapy. Unfortunately, there are no established treatments for mild cognitive impairment (MCI). Vitamin E is ineffective in treating MCI, and cholinesterase inhibitors, while possibly risky, are only minimally effective. The need for effective treatment remains expansive. The benefits of the available agents are modest, and there are currently no treatments for individuals with memory impairment who do not yet meet the diagnostic criteria for AD.

As disease-modifying therapies near realization, there are concerns about the criteria by which these therapies will be judged. It is not yet clear what kind of evidence (clinical, biomarker, or otherwise) will be required to support a disease-modifying claim. When such a drug is approved, regulators must be certain that the claims in the label are factual and unambiguous, yet a definition for “disease modification” remains to be established. One strong potential definition is: “a therapy that affects the underlying pathology and structure of the disease”. However, this is only one possibility, and a consensus definition must be codified before criteria to evaluate it can be determined.

There is room for informed speculation, however. Criteria to evaluate disease-modifying effects have been proposed, and typically involve one of two approaches (neither of which has yet been endorsed by regulators). The first is a clinical approach, in which clinical designs are employed that would ideally force a conclusion that a drug has a disease-modifying effect. In one proposed design, patients would be randomized to drug or placebo for an appropriate duration. At the end of that period, and if a difference in outcome between drug and placebo on an appropriate clinical measure or measures has been achieved, patients originally randomized to drug would then be treated with placebo, while patients originally treated with placebo would remain on placebo.

Attention-deficit/hyperactivity disorder (ADHD), once considered to be a childhood disorder, is diagnosed in ~7 million adults in the United States, as reported by The National Comorbidity Study. Although it is now recognized that ADHD often persists into adulthood, the current diagnostic criteria is geared toward symptom identification in children. Symptoms of inattention, impulsivity, and hyperactivity evolve over the life cycle and present differently in adults. Further complicating diagnosis is that ADHD is associated with multiple functional impairments and comorbid psychiatric disorders. The Multi-Modal Treatment Study of ADHD reported that only 32% of the study population had ADHD alone; 29% had ADHD plus oppositional defiant disorder and/or conduct disorder, 14% had ADHD plus anxiety or depression, and 25% had all three disorders. Optimal treatment utilizes amulti-modal approach including behavioral treatments combined with pharmacologic treatment strategies. Food and Drug Administration-approved medications for ADHD include the stimulants and nonstimulants, although tricyclic antidepressants and bupropion are also commonly used.

In this monograph, Craig L. Donnelly, MD, reviews the history of ADHD and discusses the pathophysiologic progression of childhood symptoms into those commonly exhibited by adults. Next, Frederick W. Reimherr, MD, reviews comorbidity of ADHD and describes the Utah Criteria as a method of diagnosing adults through recollection of childhood problems. Finally, Joel L. Young, MD, reviews treatment approaches to adult ADHD and its comorbid conditions.

Exposure and response prevention (ERP), a form of behavior therapy, is widely recognized as the most effective psychological treatment for obsessive-compulsive disorder (OCD). Cognitive therapy (meaning rational emotive behavior therapy [REBT], or the Salkovskis model for this article) has received increased attention as an effective method for OCD treatment. These methods have renewed hope for patients suffering with what had long been thought to be a treatment refractory condition. Yet many important issues require further discussion and investigation. At the Second International Conference on OCD, which was held in Guadeloupe, February 14–16, 1996, the following issues were highlighted:

1. Which psychotherapies are effective in the treatment of OCD?

2. What psychological strategies may be used to increase patient motivation during treatment?

3. Are relapse prevention strategies necessary after improvement?

4. How do economic factors affect the use of behavior therapy? How is OCD treatment uniform or varying from specialty providers to mental health generalists to primary care physicians? How do self-administered and therapist-administered ERP compare?

5. How does the efficacy of ERP or cognitive therapy and pharmacotherapy (either alone or in combination) compare?

6. Is ERP effective for complex forms of OCD?

7. In OCD treatment, is medication compliance improved if ERP or cognitive therapy is also used, and vice versa? How does this affect relapse rates? In addition, can doses of medications be lowered with the addition of ERP or cognitive therapy?

8. What is known about the brain function and biological changes associated with ERP and cognitive therapy?

Levodopa has played a central role in the treatment of Parkinson's disease for nearly 40 years and remains the single most effective symptomatic treatment for the disease. However, the response to levodopa therapy changes over time, and its long-term use is commonly associated with disabling motor complications. For this reason, the appropriate role of levodopa in the treatment of Parkinson's disease—in particular, the question of when to initiate therapy with the drug—has been a matter of controversy. Because levodopa is the most effective treatment for Parkinson's disease, the management of this disease becomes a matter of balancing short-term symptom control with long-term functional outcomes. This article provides an overview of the basis for levodopa-associated motor complications and their impact on patients' clinical function and quality of life, followed by a discussion of strategies for managing these complications to achieve optimum symptom control while minimizing the adverse effects of long-term therapy.

Evidence from the literature suggests that, on average, 27% of patients with a bipolar disorder (BD) experience a continuous cycling course (CCC) and that this subgroup differs significantly from patients with a noncontinuous cycling course (N-CCC) with respect to sociodemographic characteristics and clinical presentation. The aim of the present paper is to review the studies that evaluated short- and long-term treatment responses in BD patients with CCC. The retrieved studies indicate that CCC is a significant predictor of poor response to long-term treatment with lithium (the odds of a response in the CCC group were 57% less than in the N-CCC group; p<0.01), as well as to polytherapies including lithium and/or an antiepileptic augmented, when necessary, with an antipsychotic and/or antidepressant. The percentage of patients without new episodes during follow-up was significantly lower in the CCC group compared with the N-CCC group (15.4 vs. 37.6% , p<0.01). Compared with patients in the N-CCC group, members of the CCC group had a poorer response and lower remission rates after 12-week antidepressant treatments for a major depressive episode (82.3 vs. 50%, p =0.002; 69.6 vs. 40.9%, p=0.013). These findings, underlining that CCC is a predictor of poor response to short- and long-term treatment in BD, should be interpreted considering the limitations of the reviewed studies (the small sample sizes, the small number of trials and their observational nature, the lack of randomization or placebo controls, and the unblinded nature of the outcomes). Clinical trials and observational studies with larger samples are warranted to confirm the conclusions of our review.

Given the wide variety of available antidepressant therapies, an important question is how effective are we in treating depression? In clinical research trials of antidepressants, a treatment response is defined as a 50% or greater improvement in depressive symptoms, whereas remission is defined as having minimal or absent symptoms at the end of treatment. Approximately 50% of patients treated with antidepressants have a treatment response, but only about 25% have a complete remission. Many treatment responders therefore have residual symptoms despite adequate treatment. This is critically important because depressed patients with residual symptoms, even though mild in severity, still have significant functional impairment, have a high risk of relapsing into a more severe episode, and may have a more chronic course of illness. Such patients also do not show a full functional recovery from their depression. Recent comparative studies have found that remission rates are significantly higher with venlafaxine (Effexor) compared to serotonin reuptake inhibitors, which might be due to their different effects on neurotransmitter systems. The use of medication combinations, having additive and/or synergistic antidepressant effects, or adding psychotherapy following a course of pharmacotherapy also can be used to treat residual symptoms and lead to a more complete remission.