Benzodiazepines

The toxic effects of glutamate in the central nervous system are well known. This neurotoxicity occurs through metabotropic and ionotropic receptors, the latter group composed of N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), and kainate receptors. The authors investigated the neuroprotective effects of GYKI 52466, a 2,3-benzodiazepine that is a selective and potent AMPA receptor antagonist, in a rat spinal cord trauma model. Sixty Wistar albino rats were studied in three groups of 20 animals each: sham-operated controls (Group 1); spinal cord-injured rats (Group 2); and spinal cord-injured plus GYKI 52466-treated rats (Group 3). In Groups 2 and 3, spinal cord injury (SCI) was induced at the thoracic level by applying an aneurysm clip to the cord for 1 minute. One minute after the clip was removed, the rats in Group 3 received an intraperitoneal injection of 15 mg/kg GYKI 52466. Responses to injury and treatment were evaluated based on bioche...

Posttraumatic stress disorder (PTSD) can result from a traumatic experience that elicits emotions of fear, helpless or horror. Most individuals remain asymptomatic or symptoms quickly resolve, but in a minority intrusive imagery and nightmares, emotional numbing and avoidance, and hyperarousal persist for decades. PTSD is associated with psychiatric and medical co-morbidities, increased risk for suicide, and with poor social and occupational functioning. Psychotherapy and pharmacotherapy are common treatments. Whereas, research supports the efficacy of the cognitive behavioral psychotherapies, there is insufficient evidence to unequivocally support the efficacy of any specific pharmacotherapy. Proven effective pharmacologic agents are sorely needed to treat core and targeted PTSD symptoms, and for prevention. This review describes current and emerging pharmacotherapies that advance these goals.

In some situations, and particularly when intoxications are suspected, it would be advantageous if medicines and drugs of abuse could be swiftly detected in serum or urine. The Department of Clinical Pharmacology at St. Olav University Hospital has since 2004 been developing a comprehensive toxicology service (at all hours 7-days/week) for immediate quantitative analysis of between 80 and 90 substances. We here present the service in further detail and evaluate its usefulness during its first full year, 2005. Two case reports are presented to further illustrate the possible benefits of this service. Urgent testing was requested for a total of 390 samples; 351 serum and 39 urine samples. The most common indications for requesting such analyses were suspected acute intoxication (46%) and suspected therapeutic failure/adverse drug reaction (31%). 88% of the serum samples obtained for acute intoxications were positive, and 48 different substances were detected. The substances most often...

Benzodiazepines (BZ)
Classified as anxiolytics and/or anti-convulsants
Have been in clinical practice for over 40 years
Largely replaced barbiturates for anxiety-related disorders
Dependence and/or tolerance emerges after chronic BZ administration

Nocturnal panic (NP), waking from sleep in a state of panic, is a common occurrence among patients with panic disorder, with 44-71% reporting at least one such attack. NP is a non-REM event that is distinct from sleep terrors, sleep apnea, nightmares or dream-induced arousals. This review outlines recent advances in the characterization of NP, as well as current approaches to the assessment and treatment of NP. In contrast to earlier work, more recent studies suggest that patients with NP do not differ from patients without NP on sleep architecture, sleep physiology, self-reported sleep quality and severity of panic disorder. However, more precise measurement of physiological precipitants and features is warranted. Assessment of NP focuses on ruling out other explanations for NP, with differential diagnosis based on interviews, sleep polysomnography and ambulatory recording of sleep. Psychological treatment (cognitive-behavioral therapy) targets misappraisals of anxiety sensations, hyperventilatory response, and conditioned reactions to internal, physical cues. Recent evidence supports the efficacy of this approach, however, controlled studies on pharmacological agents in the treatment of NP are lacking. Research is needed to examine the effects of combined cognitive-behavioral therapy and medications, compared to medication alone in the treatment of NP.

Background: Efficient, inexpensive screening for early stage alcohol problems is important in health care settings. The Alcohol Use Disorders Identification Test (AUDIT) has been studied extensively to establish its value in this regard.Methods: A literature search that used EtOH as a database was conducted to identify studies published on the AUDIT through September 2001. Keywords used for the search were “Alcohol Use Disorders Identification Test” and “AUDIT.” All studies reporting psychometric properties of the measure were reviewed with particular attention being given to the period 1996 and later. A small number of additional references were located by noting their citation in other studies reviewed.Results: Although more research is needed on non-English versions to establish their psychometric properties, at least in its English edition, the AUDIT demonstrates sensitivities and specificities comparable, and typically superior, to those of other self-report screening measures. Test-retest reliability and internal consistency are also quite favorable. For males, the AUDIT-C, a shortened version of the AUDIT, appears approximately equal in validity to the full scale.Conclusions: Recent research continues to support use of the AUDIT as a means of screening for alcohol use disorders in health care settings in the United States.

The Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) was examined for its usefulness as a subjective measure of drug-induced parkinsonism and akathisia. Eighty-three subjects were assessed using the LUNSERS, the Simpson–Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS), before and after a 6-week treatment with olanzapine. Significant correlations were found between the changes in scores of parkinsonism items of LUNSERS and SAS. The changes in scores of akathisia item (restlessness), extrapyramidal side effects (EPS) subscale and psychic side-effects subscale of LUNSERS were significantly correlated with those of the BARS. ‘Shakiness’, one item of the EPS subscale of LUNSERS, correctly classified between parkinsonism and non-parkinsonism groups with 81.0% accuracy. A combination of four items included in EPS and psychic side-effect subscales of LUNSERS identified akathisia and non-akathisia groups with 76.2% accuracy. These results suggest that the EPS and psychic side-effect subscales of LUNSERS may be useful in screening for drug-induced parkinsonism and akathisia. Copyright © 2004 John Wiley & Sons, Ltd.

Comprehensive management of panic disorder involves a wide array treatments and interventions to reduce symptoms and increase functionality. This chapter provides an overview of the pharmacologic treatment of panic disorder including aspects of assessment, treatment selection and the biologic mechanisms of the illness.

What is the best approach for treating patients with social phobia (social anxiety disorder) over the long term? Social phobia is the most common anxiety disorder, with reported prevalence rates of up to 18.7%. Social phobia is characterized by a marked and persistent fear of being observed or evaluated by others in social performance or interaction situations and is associated with physical, cognitive, and behavioral (ie, avoidance) symptoms. The onset of social phobia typically occurs in childhood or adolescence and the clinical course, if left untreated, is usually chronic, unremitting, and associated with significant functional impairment. Social phobia exhibits a high degree of comorbidity with other psychiatric disorders, including mood disorders, anxiety disorders, and substance abuse/dependence. Few people with social phobia seek professional help despite the existence of beneficial treatment approaches. The efficacy, tolerability, and safety of the selective serotonin reupt...

Conducting toxicology on post-mortem specimens provides a number of very significant challenges to the scientist. The range of additional specimens include tissues such as decomposing blood and other tissues, hair, muscle, fat, lung, and even larvae feeding on the host require special techniques to isolate a foreign substance and allow detection without interference from the matrix. A number of drugs

This study examined specific predictors of the efficacy of risperidone (RP), olanzapine (OL) and first-generation antipsychotic agents (FGAs), the role of confounding factors, and concomitant agents such as antidepressants, anxiolytics, and mood stabilizers in the treatment of health related quality of life (HRQL) impairment of schizophrenia patients.This was a community-based, open label, parallel group naturalistic study of 124 schizophrenia outpatients who received either RP, OL, FGA, or combined agents (CA). Evaluations were performed at baseline and 12 months later. They included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Positive and Negative Syndrome Scale (PANSS), the Distress Scale for Adverse Symptoms, and inventories for the assessment of distress severity, subjective tolerability, and self-efficacy.OL was found to be superior to RP, FGAs and CA in terms of quality of life. FGAs revealed greater therapeutic benefit than RP, which was more beneficial than combined therapy. Improvement in Q-LES-Q was revealed in patients who received antidepressants and anxiolytics, but not mood stabilizers, or anti-Parkinson drugs. This effect was independent of treatment groups and gender. Regression models revealed that changes in emotional distress and side effects were common predictors for HRQL changes across treatment groups. Specific predictors of HRQL efficacy included self-efficacy for OL, negative and positive symptoms for RP, dysphoric mood and positive symptoms, daily doses and self-efficacy for FGA treated patients.These findings suggest that OL is beneficial in the treatment of HRQL impairment in schizophrenia compared with RP, FGAs and CA. Special attention should be paid to specific predictors of HRQL efficacy for each antipsychotic agent, and to concomitant treatment with antidepressants and anxiolytics.

Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes ...