Systematic investigations indicate that some of the recognized psychiatric disorders can be identified among those with mental retardation due to chromosomal abnormalities. We report a psychotic patient with mild mental retardation (intelligence quotient: 68) and minor anomalies that had a chromosomal aberration not previously described in a psychotic patient. Our patient highlights the importance of the cytogenetic study in psychiatric patients with comorbid mental retardation or minor anomalies. In addition, her psychosis symptoms may be helpful to propose a new candidate gene for psychosis.

This discussion focuses on the historical trends of carbamazepine in the treatment of acute mania, acute bipolar depression, and as maintenance treatment for bipolar disorder. Clinical implications of efficacy, safety, tolerability, and drug interactions associated with carbamazepine are discussed as well.

Important progress in bipolar disorders therapeutics began in the 1970s with lithium and the conventional antipsychotics, and continued in the 1980s with carbamazepine, in the 1990s with divalproex, and in the 2000s with lamotrigine and the introduction of the atypical antipsychotics. Electroconvulsive therapy (ECT) has been used throughout these periods and still has a place in bipolar disorder, especially for severe, treatment-resistant, and very acute cases.

Immediate-release carbamazepine was first approved for epilepsy in 1974, followed by approval of carbamazepine extended release capsules (CBZ ERC) for epilepsy in 1997. Reports of carbamazepine use in bipolar disorder began in 1973 in Japan, when Okuma and colleagues reported antimanic efficacy in manic-depressive psychosis. In 1978, Ballenger and Post reported effective use of carbamazepine in bipolar illness. The initiation of CBZ ERC in bipolar disorder trials began in 2001. In 2004, CBZ ERC received Food and Drug Administration approval for the treatment of acute manic and mixed episodes in patients with bipolar disorder (Slide 4).

In 1988, a survey of American psychiatrists reported moderate-to-marked effectiveness for carbamazepine for the following conditions: partial complex seizures (85%), generalized seizures (82%), trigeminal neuralgia (81%), mania prophylaxis (72%), acute bipolar depression (67%), intermittent explosive disorder (65%), acute mania (62%), and schizoaffective disorder (58%). Historically, carbamazepine has been considered superior to lithium for rapid cycling and mixed mania, bipolar II disorder, bipolar disorder not otherwise specified (NOS), and bipolar disorder with mood incongruent delusions or comorbidity. In multiple controlled trials, carbamazepine was as effective as lithium in the treatment of acute mania. Limitations of early controlled carbamazepine trials include lack of parallel placebo groups, small samples (commonly <60 subjects), confounds of concomitant treatments, and low doses used to avoid/attenuate adverse effects.

A 30-year-old woman with severe pathological gambling and cyclothymia presented to our program with no previous history of pharmacologic or psychotherapeutic treatment. Pathological gambling is an impulse-control disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) in which comorbidity is common, particularly with substance abuse, obsessive-compulsive disorder and mood disorders. As described in this case, pathological gamblers with bipolar comorbidity may be effectively treated with mood stabilizers such as lithium. After receiving 10 weeks of lithium treatment, the patient showed improvement in both gambling behavior and affective instability. The identification of specific subtypes among patients with pathological gambling may be relevant to the choice of pharmacologic treatment.

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.

Neuropathic pain and fibromyalgia are prevalent diseases which have major consequences on healthcare resources and the individual. From the clinical point of view neuropathic pains represent a heterogeneous group of aetiologically different diseases ranging from cancer to diabetes. Patients with fibromyalgia also display clinical features common in neuropathic pain suggesting that there might be some overlap. The mechanisms responsible for symptoms and signs in both diseases are still unknown. Recently, there have been numerous reports of various pharmacological treatments of neuropathic pain and fibromyalgia with often disappointing results. Most of the studies were of short duration, had high attrition rates, and displayed other methodological problems. Some compounds had high rates of adverse effects which makes it often difficult for the patients to tolerate the treatment, especially in the long-term. At present, the best options for medication treatment are tricyclic antidepressants in lower dosage than usual in psychiatric disorders and a wide range of anticonvulsants. Opioids are sometimes recommended but have been found to have minor efficacy. Recently, there have been more controlled trials, which are reported here if they had been published between 2002 and 2004. Various compounds have been tested in different studies. Treatment of fibromyalgia, which has many features in common with depressive symptoms, became the focus of interest. New promising studies with dual serotonin-norepinephrine reuptake inhibitors (duloxetine and milnacipram) and a newer antiepileptic drug (pregabalin) are in progress. Future research will have to apply new approaches (eg, using a mechanism based classification of neuropathic pain and carrying out studies in populations with the same symptom but not necessarily the same disease) in order to find effective treatments for these common and often debilitating diseases.

Multiple sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. Although Charcot noted behavioral changes associated with MS, nearly a century would elapse before researchers began defining their full extent and severity. Broadly speaking, abnormalities may be divided into those of mood and cognition. Many patients are afflicted with both and it is essential that clinicians are not only aware of this but understand how to detect problems and provide treatment.

The lifetime prevalence of major depression in MS patients approaches 50%. As Scott B. Patten, MD, and colleagues note, these data came from specialist clinics with the potential for ascertainment bias. Shifting their inquiry into a large community-based sample, they report that the rates of mood disorder remain elevated largely in younger MS patients. While it is partly reassuring to find that aging comes with at least one benefit, the gist of this study is to reinforce the message that clinically significant depression is a problem for MS patients. Not only does it adversely affect quality of life and lead to increased suicidal thinking, it exerts more subtle deleterious effects as Peter A. Arnett, PhD, reveals. In a longitudinal study exploring the relationship between depression and cognition, Arnett reports that MS patients with prominent evaluative symptoms of depression (ie, feelings of inferiority, failure) have greater difficulty with cognitive tasks that encompass information processing speed and executive function linked to working memory. A preoccupation with negative thoughts may reduce the cognitive capacity necessary for aspects of attention and working memory.

These data complement the review article of Ralph H.B. Benedict, PhD, ABPP-CN, that focuses on methods of detecting cognitive dysfunction in MS. As with mood disorders, impaired cognition has been linked to difficulties with work, relationships, and, in more extreme cases, basic activities of daily living. Usually, the more subtle pattern of deficits associated with demyelination differ from those seen in cortical-type dementias and will be missed should clinicians rely on screening instruments like the Mini-Mental State Examination. At the same time, the method of choice for eliciting deficits, namely neuropsychological testing is expensive and frequently not readily available. This has meant that alternative instruments, like the Multiple Sclerosis Neuropsychological Screening Questionnaire, assume an added prominence. With good sensitivity, specificity, and ease of administration this informant based scale makes a useful addendum to the neurological examination. It is in the same light that the magnetic resonance imaging (MRI) rating scale by Laury Chamelian, MD, FRCPC, and colleagues should be viewed.

Behavioral and psychological symptoms of dementia pose significant challenges in the management of patients with Alzheimer's disease. Neuropsychiatric symptoms are associated with cognitive decline, highly impaired activities of daily living, and frontal lobe pathology. Moreover, behavioral and psychological symptoms can diminish patient quality of life, increase caregiver distress, and accelerate nursing home placement. Although these symptoms are often associated with the later stages of Alzheimer's disease, a high percentage of individuals with mild cognitive impairment or mild Alzheimer's report symptoms as well. This article provides an overview of behavioral and neuropsychiatric symptoms associated with Alzheimer's disease and discusses nonpharmacologic and pharmacologic approaches to the management of such symptoms. For patients with severe behavioral and psychological symptoms of dementia, pychotropic agents may be warranted, whereas approved therapies for Alzheimer's, including cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine, may be appropriate in less severe cases.

Evelyn is a 35-year-old woman who presented to a psychiatrist with complaints of marriage difficulties. As she described some of these difficulties, she leaned forward, and her psychiatrist responded by changing her body posture and unfolding her arms. Evelyn explained that she had been brought up to be stoic in the face of difficulties. When she described some of the family's early circumstances, her expression became sad and her psychiatrist responded by furrowing her brow. Evelyn's parents had encouraged the kids to be self-reliant and independent; problems were not complained about, they were simply dealt with. At present, however, her situation felt overwhelming. She felt embarrassed to have to talk with a stranger about her marriage. Her psychiatrist reflected back, saying that her early family had obviously given her many strengths, and that it must be difficult to have to ask for help. At that point in the conversation, Evelyn's eyes misted over with tears.

When benzodiazepines (BZs) supplanted barbiturates as a favored, safer treatment for anxiety and sleep disorders in the 1960s, the abuse liability and dependence potential of these drugs were little understood. Widespread recognition of the difficulty of stopping use of chronically taken BZs emerged through the popular press in the late 1970s, which resulted in reluctance to prescribe these otherwise clinically useful compounds. Evolution of the understanding of the biochemical basis for BZ effects in the 1980s and 1990s, coupled with regulatory emphasis on collection of data used in legal scheduling decisions, made possible a targeted search for drugs that would provide effective treatment for anxiety disorders in the absence of abuse liability or dependence potential. Compounds that have selective efficacy at subtypes of the γ-aminobutyric acid type A receptor, are active in preclinical anxiolytic screens, but negative in preclinical studies of behavior relevant to evaluation of abuse liability appear to be one promising means for achieving this end.

The articles in this supplement demonstrate that ethnicity and ethnopharmacology have emerged as important considerations in the treatment of patients with mental illness. Patients from ethnically diverse backgrounds often demonstrate varying levels of response and tolerability to drugs such as atypical antipsychotics. In part, this response may be due to the particular agent itself, yet metabolic differences between populations may also impact these varied effects. Specific isoforms of the cytochrome P450 enzyme system can dictate the rate at which patients metabolize certain medications, thus genotypic variability among these enzymes predicts the phenotypic response or metabolic rate. For example, patients from certain ethnic groups such as Caucasians and Hispanics tend to be extensive metabolizers, while African Americans and Asians tend to be slower metabolizers.

Total dose and resulting plasma drug levels are closely related to adverse effects. Thus, patients exhibiting slow or poor oxidative enzyme activity may face increased drug exposure and potentially higher rates of adverse events. The undesirable antipsychotic-induced side effects include metabolic issues such as weight gain, insulin resistance, and dyslipidemia. Certain ethnic groups are at a higher risk for developing these metabolic problems. Side effects such as extrapyramidal symptoms and tardive dyskinesia, which have traditionally been attributed to conventional antipsychotics, may occur with atypicals although much less frequently. Movement disorders caused by the use of an atypical antipsychotic become particularly apparent when plasma drug levels are high. Patients with a slow metabolism will be exposed to high plasma drug levels, even on standard dosages of an atypical antipsychotic.

Therefore, given a genetic predisposition and the potential for metabolic side effects with atypical antipsychotics, a careful risk/benefit assessment is crucial for the successful management of patients with mental illness.

Other patient factors as well as clinician factors can influence the response and tolerability of treatment. Provider biases can affect access to certain medications, while misconceptions about how to treat certain ethnic groups can affect the initial choice of medication and dosage. Ultimately, sensitivity and an awareness of pharmacologic issues as they relate to an expanding and ethnically diverse population must become a high priority for clinicians treating patients with atypical antipsychotics. Side effects of these medications can be minimized with vigilance and a thorough understanding of the risks and benefits.

Continued research is necessary to further understand the field of ethnopharmacology and to lead psychiatry into the future of individualized, metabolically directed therapies.