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.

Seventeen years after professional baseball player Jim Eisenreich first developed symptoms of Tourette syndrome (TS), the correct diagnosis was finally made.

At age 6, his rapid eye blinking led to a diagnosis of hyperactivity. “I was told I would grow out of it,” says the 39-year-old Eisenreich, who may have played his last game as a Los Angeles Dodger. “I knew I was different even then.”

In the early 1980s, Eisenreich's condition first became public. Since then, his achievements as a professional athlete have made him a role model for other TS patients.

Sports were always a haven for him as he grew up. “I found peace, comfort, and security in sports. Whatever the season, I played the sport—football, baseball, hockey,” says Eisenreich. “Socially, I didn't go to the movies or go out much with girls.”

After 2 years in the minor leagues, he was called up by the Minnesota Twins in 1982 as an outfielder. During the season, a TS specialist recognized his grunting and sniffling as signs of the disease. “I had no idea what the specialist was talking about, and the Twins doctors dismissed it because I didn't have copralalia,” he says. The Twins team physician (an internist) prescribed a sedative. Then Eisenreich tried Inderal, which caused hyperventilation, and Catapres, which caused depression.

Parkinson's disease is the most common basal ganglia disorder that is caused by the degeneration of dopaminergic neurons in the substantia nigra. This article reviews the normal physiology of the basal ganglia in the normal state, as well as the pathophysiology of Parkinson's disease (PD) and other movement disorders associated with the basal ganglia. Also discussed is the pathophysiological basis for the surgical treatment of PD.

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.

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.

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.

There are several important issues regarding the manner in which medications are tested prior to their release and monitored after approval that must be appreciated in considering issues related to cardiovascular safety of medication treatments for attention-deficit/hyperactivity disorder (ADHD) in adults. First, patients treated in clinical trials are not necessarily representative of those seen in practice settings, as specific inclusion/exclusion criteria in studies limit a variety of psychiatric, medical, and social factors that could potentially introduce confounds related to the collection and/or interpretation of efficacy, tolerability, and safety data. However, many of these factors are present in patients treated in clinical practice. In addition, the manner in which medications are administered in clinical trials does not necessarily replicate the way they are used in the community. Often, there are differences in titration schemes and dosing options. Also, in clinical trials, drugs are rarely studied in combination, although they are often used in this manner in practice settings. Further, Phase III clinical trials (at least in psychiatry) often do not enroll a large enough sample to evaluate infrequently occurring adverse events. Rather, the predominance of information regarding rare side effects is derived from voluntary reports made after a drug comes to market—and therefore likely under-reports the phenomenon. Finally, information regarding drug safety that comes to practitioners in the form of medication warnings or advisories may reflect concerns that extend beyond the strict interpretation of clinical trials data. These and other issues represent major obstacles in attempting to fully understand issues related to safety and tolerability of medication in “real world” settings.

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.

The proprietary, immediate and extended drug delivery technologyLiquiXR® utilizes an ion-exchange resin that complexes with amphetamine or any active moiety that can be protonated and is water-soluble. The active ingredient of the drug product forms a complex with an ion exchange polymer of the resin resulting in micron-sized particles. A portion of these particles is then coated with an aqueous, pH-independent polymer designed to provide sustained release of drug product. The polymer coating applied to the ion-exchange resin particles is of varying thickness, allowing for extended release of active drug while uncoated particles provide for immediate release of drug.

The micron-sized particles lend themselves to being formulated into an appropriate dosage form: solid/chewable tablet, liquid suspension, orally disintegrating tablet, film, or capsules. Active ingredient of drug product is subsequently released from the dosage form in millions of particles, with release driven by a combination of ion exchange and diffusion. After drug release, the ion-exchange resin particles are excreted in the feces.

The release characteristics of LiquiXR allow for customized, sustained release of active drug ∼24hours post dose. Mechanistically, drug particles enter the gastrointestinal (GI) tract. As positively-charged ions from GI fluids diffuse across the coating, it displaces drug ions from product and they diffuse through the coating and into the GI fluids for absorption. As the coating is of variable thickness, some drug product takes longer to diffuse and absorb, providing for the delayed drug release characteristics.

The LiquiXR drug delivery technology has already been successfully utilized in the development of treatment options (liquid suspension and chewable tablet) that offer rapid absorption and sustained plasma levels after once-daily dosing. LiquiXR is utilized in Dyanavel® XR (amphetamine extended-release oral suspension; AMPH EROS), which is indicated for treatment of ADHD. It comprises 2.5mg/mL amphetamine base and uses LiquiXR technology to provide an immediate release component followed by an extended-release profile.

Efficacy of AMPH EROS was established in children 6 to 12 yr in a Phase 3, placebo-controlled laboratory classroom study. In that study, ADHD symptoms in children on an individually optimized dose of amphetamine (range 10–20mg/day) were statistically significantly improved compared with symptoms in children treated with placebo. For children treated with AMPH EROS, onset of effect was demonstrated at 1hour after dosing, and efficacy was observed through 13hr post-dose. The effect size (ES) was comparable to ES demonstrated for other psychostimulants tested in studies using a similar design. The efficacy data reported for AMPH EROS provides an excellent example of the potential utility and clinical application for other active drug products requiring an immediate and extended release profile.

Funding Acknowledgements: Support provided by Tris Pharma, Inc.

Opioid use disorder (OUD) is a major public health problem in the United States. It has resulted in devastating consequences for people with this condition, including psychosocial and legal problems, in addition to contraction of infectious diseases such as HIV and hepatitis B and C. Furthermore, this disease can cause fatalities from drug overdoses and drug–drug interactions. OUD shatters families and destroys relationships. Effective treatment is crucial in order to curtail the consequences of this condition. The objective of this article is to provide a review of the pharmacotherapies currently being used to treat OUD.