Anxiety disorders are among the most prevalent psychiatric disorders in the general population, found nearly twice as often in women, and estimated to affect 26.9 million individuals in the United States alone. Anxiety disorders are associated with considerable chronicity, morbidity, and disability. Treatment of anxiety disorders includes pharmacologic and nonpharmacologic approaches. The first-line pharmacologic treatments currently include the use of serotonin reuptake inhibitors and selective serotonin reuptake inhibitors. However, despite the general success of the available treatments, no single anxiolytic appears to be effective for all patients suffering from anxiety. Low recovery rates have been reported in all anxiety disorders, underscoring the need for optimizing treatment for these disabling disorders. In recent years, there is increasing interest in the use of atypical neuroleptics in the treatment of anxiety disorders patients. This article discusses the emerging data on the use of these agents in the treatment of anxiety with a focus on treatment-refractory patients and on the implications for the treatment of women suffering from anxiety disorders.

Alzheimer's disease is a progressive, neurodegenerative condition characterized by deficits in cognition, inability to perform activities of daily living, and alterations in behavior. Galantamine hydrobromide is the newest acetylcholin esterase inhibitor (AChEI) approved in the United State for the treatment of mild-to-moderate AD. The safety and efficacy of galantamine has been demonstrated in multiple randomized, Phase III trials of > 2,600 patients with mild-to-moderate AD. Studies have found that galantamine improved or maintained performance in all domains of AD (cognition, function, behavior, and caregiver burden in the short term and slowed the decline in performance or maintained baseline performance through 12 months. The dual mechanism of action may make galantamine a reasonable treatment option for both newly diagnosed patients and patients who have not benefitted from or have poorly tolerated current therapy.

Sexual dysfunction related to antidepressants, particularly serotonin reuptake inhibitors is a major cause of premature treatment discontinuation. This places patients at increased risk for recurrence, relapse, chronicity, and mortality (eg, suicide). The clinical assessment requires a comprehensive evaluation of sexual function, including libido, arousal, orgasm, and resolution prior to affective disorder, disturbances associated with the emergence of depression, and changes or dysfunctions associated with antidepressant treatment. Other factors to be included for evaluating sexual dysfunction include inquiry for concurrent medical conditions, somatic treatments, lifestyle risk factors, and response to antidepressants. Current treatment approaches to antidepressant-associated sexual dysfunction have relied on open-label reports, literature reviews, and clinical wisdom. Without double-blind, placebo-controlled studies to support them, too much non-evidence-based treatment may be offered to patients. Advances into nonadrenergic-noncholinergic novel signal transduction, specifically phosphodiesterase type-5 inhibitors, offer new opportunities for developing evidence-based treatments for this side effect and improving depression disease management outcomes.

The proportion of pregnancies exposed to either second-generation antipsychotics (SGAs) or first-generation antipsychotics (FGAs) varies between 0.3%–2% of all pregnancies, but, until now, little is known about the potential neurobehavioral teratogenicity of antipsychotics. Assessing this safety facet is the aim of this article. PubMed, Scopus, and Google Scholar were searched for eligible articles. PubMed (1954 to May 2016) was searched using several medical subject headings, variously combined. PubMed search results were also limited using the search filter for human studies published in English. Scopus and Google Scholar searches were filtered for article title (antipsychotics/neuroleptics, pregnancy). After excluding duplicates, 9,250 articles were identified and 29 met the following inclusion criteria: only articles that provided original/primary data on neurodevelopmental outcome in human offspring older than 4 months of age, independently of the study design, were selected for review. Indeed, some relevant neurodevelopmental milestones are achieved at this time. Length of study and neurodevelopmental assessment methodology did not influence the study selection. Unfortunately, published data on neurodevelopmental teratogenicity of SGAs mainly derive from case reports and small case-series studies. Even findings emerging from case-control and prospective/retrospective studies are of limited clinical relevance because of their small sample sizes. Limited data are also available on FGAs. Hence, we have to conclude that the long-term neurodevelopmental outcomes for children exposed in utero remain unclear. Low to very low quality evidence of retrieved data makes impossible to confirm or exclude potential long-lasting untoward effects on infant neurocognitive development associate with antenatal exposure to either SGAs or FGAs.

As with members of other cultural and religious groups, patients within the Orthodox Jewish community present with their own distinct clinical psychiatric issues related to their unique beliefs and practices. This article reviews the existing literature and anecdotal experience on the psychopharmacologic assessment and treatment of Orthodox Jewish patients. Specific aspects examined include this group's perceived intense stigma in receiving treatment, the priority this community places on cognitive functioning, and how the influence of Jewish laws on marriage and sexual practices impacts one's treatment decisions. The relevance of Jewish dietary laws, the Sabbath, and the community's interest in alternative treatments are also discussed. The limited ethno-psychopharmacology research related to Orthodox Jewish psychiatric patients is reviewed. We conclude that understanding issues such as these is critical if one is going to work within this cultural system in order to successfully address their mental health issues. However, the dearth of controlled research in this community needs to be addressed to provide more effective treatment.

The issues surrounding generic drug substitution in patients with epilepsy are complex.The substitution of one formulation of an antiepileptic drug (AED) for another is controversial. Well-reasoned and defensible cases can be made both for and against such substitution. Although regulatory agencies require that generic and proprietary drugs have similar pharmacokinetic bioequivalence data, their therapeutic efficacy may not necessarily be identical. The paroxysmal nature of epilepsy, the narrow therapeutic index of some AEDs, the need to. individualize therapy to achieve seizure control, and the negative consequences of uncontrolled epilepsy distinguishes epilepsy from other clinical conditions. Epilepsy management with AEDs requires careful dose titration and consistent drug exposure at the optimal level for each patient, which can be altered if a different formulation of the AED is substituted. Unexpected variability in plasma concentrations could occur when a patient who has been receiving one formulation of an AED (generic or brand) receives an alternate formulation.Thus, no substitutions should be made for people with epilepsy without the knowledge and approval of the prescribing physician. Patients should be consulted about the substitution, with all risks and benefits carefully explained.

The origins of the word “shame” recall the concept of the infraction of integrity both as scandal and as individualization. The human experience of shame stretches along a continuum from modesty to disabling interpersonal terror. Unlike other basic affects, its emergence is a fundamental moment in the process of self-awareness and self-object differentiation. Neglected by psychiatry because it was regarded as a moral concept, today it is possible to hypothesize that it has a biologic basis that one can attempt to describe in terms of corticothalamic pathways. In this respect, like other affects, it could be considered as a cognitive shortcut to activate specific and evolutionally useful behavioral patterns, such as concealment or a request for affiliation. It is fairly ubiquitous in psychopathology, but is clinically much more structured in its abnormal expressions in anxiety disorders, particularly social phobia, obsessive-compulsive disorder, eating disorders, body dysmorphic disorder, and even in bipolar mood disorder. In schizophrenia it has been described as being one stage in the construction of delusion. Its presence is connected to interpersonal relationship (altruism) though it seems absent in autism. The assessment of shame experiences in psychiatric patients could be useful for both pharmacological and psychotherapeutic strategies, and could provide a categorization of a new psychopathology based on abnormal affects.

Pharmacotherapy of multiple sclerosis (MS) is evolving rapidly. Despite impressive gains over the past 2 decades in the approval of multiple drugs for MS, lack of recruitment of minorities with MS in phase 3 clinical studies is a persistent concern and skews efficacy and disability data.

Modern formulations of psychiatric disorders hypothesize that mother nature goes awry, causing both genetic and epigenetic disease actions. Genetic disease actions are the consequences of naturally inherited risk genes that have an altered sequence of DNA. This altered DNA sequence theoretically leads to the production of altered gene products in neurons, causing inefficient information processing in various brain circuits, and biasing those circuits towards developing symptoms of a mental illness. Epigenetic disease actions are theorized either to activate risk genes to make an altered gene product or to activate normal genes to make normal gene products but at the wrong time. Epigenetic disease mechanisms theoretically turn normal genes into risk genes by causing normal genes to be expressed in neurons when these genes should be silenced or by causing normal genes to be silenced when they should be expressed.

Attention-deficit/hyperactivity disorder (ADHD), the single most common neuropsychiatric disorder with cognitive and behavioral manifestations, often starts in childhood and usually persists into adolescence and adulthood. Rarely seen alone, ADHD is most commonly complicated by other neuropsychiatric disorders that must be factored into any intervention plan to optimally address ADHD symptoms. With more than 30 classical Schedule II (CII) stimulant preparations available for ADHD treatment, only three nonstimulants (atomoxetine and extended-release formulations of clonidine and guanfacine) have been approved by the United States Food and Drug Administration (FDA), all of which focus on modulating the noradrenergic system. Given the heterogeneity and complex nature of ADHD in most patients, research efforts are identifying nonstimulants which modulate pathways beyond the noradrenergic system. New ADHD medications in clinical development include monoamine reuptake inhibitors, monoamine receptor modulators, and multimodal agents that combine receptor agonist/antagonist activity (receptor modulation) and monoamine transporter inhibition. Each of these “pipeline” ADHD medications has a unique chemical structure and differs in its pharmacologic profile in terms of molecular targets and mechanisms. The clinical role for each of these agents will need to be explored with regard to their potential to address the heterogeneity of individuals struggling with ADHD and ADHD-associated comorbidities. This review profiles alternatives to Schedule II (CII) stimulants that are in clinical stages of development (Phase 2 or 3). Particular attention is given to viloxazine extended-release, which has completed Phase 3 studies in children and adolescents with ADHD.

Over the past century researchers have attributed the symptoms that today are labeled as Tourette syndrome to various etiologies. Although most investigators have accepted Gilles de la Tourette's initial description of a symptom complex of tics and involuntary vocalizations, most have rejected his claim that “tic disease” resulted from hereditary degeneration. Subsequent investigators have offered an array of contradictory etiological explanations including viewing these symptoms as a subset of choreas, a result of insufficient inhibition, a failure to control infantile habits, a sequel to encephalitis and other infections, or the result of unconscious psychosexual childhood conflict. With the advent of effective pharmacologic treatments in the 1960s, psychiatrists, often urged on by the parents of afflicted children, began to insist that the disorder resulted from organic factors, most likely connected to transmission of the neurotransmitter dopamine and signaling in the basal ganglia. Since the 1970s, research has focused on a variety of possible organic substrates, but disputes over which symptoms to include in the syndrome's phenotype continue to constrain efforts to locate its etiology.

Obsessive-compulsive symptoms (OCS) are relatively common and clinically significant phenomena in schizophrenia patients, suggesting the existence of a separate schizo-obsessive subgroup of the disorder. Although a majority of schizo-obsessive patients have typical ego-dystonic OCS, a meaningful proportion exhibits diagnostically challenging psychopathological phenomena, psychotic in content and obsessive in form. We report the clinical and functional magnetic resonance imaging characteristics of a schizophrenia patient who developed auditory hallucinations with musical content and obsessive in form. We suggest that “obsessive musical hallucinations”, that integrate both psychotic and obsessive-compulsive disorder (OCD)-related features, may be mediated by the brain networks believed to be involved in OCD and in auditory musical hallucinations.

Platelet dysfunction and thrombocytopenia rarely occur during clozapine therapy, but constitute an important source of morbidity and mortality if they are not detected and therapy is discontinued. The manufacturer recommends discontinuing clozapine when the platelet count falls below 100,000/μL and resuming therapy when the count returns to within normal range (150,000–450,000/μL). If thrombocytopenia recurs, clozapine should be permanently discontinued.

The authors report a rare case of long-term thrombocy-topenia persisting 40 months postclozapine treatment. In addition, increased in vitro platelet [14C] serotonin release was observed in the presence of the drug, suggesting an immune-related cause for the thrombocytopenia.

G.W., a 43-year-old African-American man, had been treated in the South Carolina Department of Mental Health since 1974 with a diagnosis of schizophrenia of chronic undifferentiated type, along with severe paranoid, delusional, threatening, and assaulting behavior. There was no history of illicit drug use. He had received intramuscular fluphenazine deconoate and haloperidol, as well as other neuroleptics, with little benefit observed during his years of treatment.

Clozapine was initiated at 25 mg bid on July 2, 1993, and was gradually increased to 650 mg daily over the next 20 months. After 7 weeks on this dose, the patient's platelet count fell from 103,000/μL to 60,000/μL, and clozapine was discontinued. A week later, the count had improved to 109,000/μL; 3 weeks later, with the platelet count at 109,000/μL, clozapine was reintroduced and titration started. However, within 7 days, his platelet count fell to 70,000/μL and clozapine was permanently stopped.