Treatment of selective mutism: focus on selective serotonin reuptake inhibitors

Abstract Selective mutism is a pediatric psychiatric disorder that occurs when a child consistently fails to speak in specific situations in which speaking is expected, such as at school and social gatherings, but speaks appropriately in other settings. Selective mutism often is diagnosed when a child starts school and does not talk to teachers or peers, but talks to family members at home; the condition is frequently accompanied by anxiety and shyness. Although the underlying etiology of the condition remains unclear, psychotherapy is the preferred initial treatment, with the support of parents and teachers. If the child does not respond to psychotherapy, addition of pharmacologic treatment should be considered, depending on the severity of symptoms and presence of other illnesses. Although data are limited to case reports and trials with small patient populations and short follow-up periods, some patients with selective mutism respond to therapy with selective serotonin reuptake inhibitors (SSRIs). Fluoxetine is the most studied SSRI as treatment for the condition, although further investigation is required to determine the optimal dosage and duration of therapy.     

Akinesia and mutism following a methylphenidate challenge test

A case of akinesia and mutism is described in a menopausal, depressed woman with onset following a mood challenge with 40 mg of methylphenidate taken orally over a 3-hour period. Various diagnoses are considered with preference given on clinical grounds to conversion disorder precipitated by drug-induced dysphoria. It is suggested that increased susceptibility to dysphoria may have been related to prior clomipramine administration and hypoestrogenism.     

Reversible akinetic mutism possibly induced by baclofen

A 76-year-old man developed akinetic mutism after 3 days of receiving low-dosage baclofen. Electroencephalography showed a diffusely slow background with intermittent generalized sharp wave discharges. The condition resolved after discontinuing baclofen. To our knowledge, this is the first reported case of baclofen-induced akinetic mutism in a patient with normal renal function. The pathophysiology of this condition is unknown, but it may result from selective binding of the drug to the gamma-aminobutyric acid-B receptors located in the frontal lobes or thalamic nuclei, interrupting the thalamocortical limbic pathways.     

Tyramine infusions and selective monoamine oxidase inhibitor treatment

The relationship between changes in IV tyramine pressor sensitivity accompanying selective monoamine oxidase (MAO) inhibitor treatment and estimates of MAO-A and MAO-B inhibition in vivo were studied. Reductions in platelet MAO activity provided an index of MAO-B inhibition, while changes in plasma 3-methoxy-4-hydroxyphenethylene glycol (MHPG) were used as an hypothesized reflection of MAO-A inhibition. Chronic treatment with the MAO-A inhibitor clorgyline and the MAO-B inhibitor pargyline showed significant inhibition of the alternate MAO enzyme as well, although this crossover effect was greater for pargyline than clorgyline. The MAO-B inhibitor deprenyl appeared to maintain the greatest degree of MAO inhibition selectivity in vivo. Tyramine pressor sensitivity changes accompanying administration of the MAO inhibitors were highly correlated with decreases in plasma MHPG (r=0.92), supporting our previous data indicating the rank order of clorgyline > pargyline > deprenyl for enhancement of tyramine pressor sensitivity and, thus, suggesting that tyramin potentiation is primarily a function of MAO-A rather than MAO-B inhibition. Changes in plasma MHPG are suggested to provide a potentially useful clinical index of in vivo MAO-A inhibition.Presently with the Biological Psychiatry Branch, NIMH     

Phenomenology of adolescent inhalant intoxication

Although volatile substance inhalation is prevalent in many contexts and presents a serious threat to public health, this pernicious form of substance misuse remains poorly understood. The question of why people seek and misuse inhalants may be addressed by examining phenomenological accounts of inhalant intoxication, yet few investigations of inhalant intoxication experiences are reported in the literature. This investigation employed a structured interview to assess inhalant intoxication experiences of 267 low-, moderate-, and high-frequency inhalant users. Low-frequency inhalant users reported predominately hedonic experiences during inhalant intoxication, whereas high-frequency users reported a mixture of hedonic and aversive experiences. Aversive experiences such as depressed mood, suicidal ideation, and chest pain were commonly reported by high-frequency users but were relatively rare among low-frequency users. High-frequency users also experienced significantly more euphoria, talkativeness, and grandiosity during inhalant intoxication than low-frequency users. Hedonic and aversive experiences during episodes of inhalant intoxication are relatively common among high-frequency adolescent inhalant users.     

A case of mutism subsequent to cocaine abuse.

The authors report a case of mutism that was ultimately found to be associated with chronic cocaine use in an adult woman. Brain dysfunction was confirmed by SPECT scan, which revealed reduced cerebral blood perfusion and areas of infarction, presumably consequent to the cocaine addiction. This is the first reported case of such an association.     

Cyclooxygenase 2 selective inhibitors in cancer treatment and prevention

Prostaglandin synthesis by a number of enzymes is important at all stages during the genesis of cancer. The availability of prostaglandin H₂ as a substrate for prostaglandin production is a critical control point in its synthesis. Cyclooxygenase (COX) occurs in two forms (COX-1 and -2) and acts as the rate-limiting enzyme that generates prostaglandin H₂. COX-1 is produced as a steady-state enzyme, while COX-2 is heavily involved in inflammation and tumorigenesis. Differences in the catalytic sites of these enzymes are utilised to generate COX-2 selective inhibitors. Certain chemical characteristics of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors make some of these inhibitors more effective against COX-2 than others. Epidemiological, animal and preclinical data demonstrate the promise of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors as anticancer agents. Ongoing clinical trials are designed to determine the efficacy of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors in the prevention and treatment of many types of cancer.     

Cyclooxygenase 2 selective inhibitors in cancer treatment and prevention

Prostaglandin synthesis by a number of enzymes is important at all stages during the genesis of cancer. The availability of prostaglandin H(2) as a substrate for prostaglandin production is a critical control point in its synthesis. Cyclooxygenase (COX) occurs in two forms (COX-1 and -2) and acts as the rate-limiting enzyme that generates prostaglandin H(2). COX-1 is produced as a steady-state enzyme, while COX-2 is heavily involved in inflammation and tumorigenesis. Differences in the catalytic sites of these enzymes are utilised to generate COX-2 selective inhibitors. Certain chemical characteristics of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors make some of these inhibitors more effective against COX-2 than others. Epidemiological, animal and preclinical data demonstrate the promise of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors as anticancer agents. Ongoing clinical trials are designed to determine the efficacy of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors in the prevention and treatment of many types of cancer.     

选择性醛甾酮拮抗药在高血压治疗中的应用

醛甾(固)酮与其受体结合后通过增加水钠潴留加重高血压。醛甾酮拮抗药分为选择性和非选择性2 大类。醛甾酮受体拮抗药不仅有助于降低血压,而且可减少醛甾酮对心血管系统的不利作用,减少心室肥厚和心血管事件的发生率。     

Role of COX-2 selective inhibitors for prevention and treatment of cancer

Cyclooxygenase-2 (COX-2) is an enzyme induced by inflammatory and mitogenic stimuli and results in enhanced synthesis of PGs in inflamed and neoplastic tissues. It is associated with cell proliferation and growth, in various cancerous conditions. We review the potential mechanisms of cancer reduction with COX-2 inhibitors and the preclinical evidence suggesting their effectiveness. Results of our study show that COX-2 is a regulatory factor for a number of pathways that can result in cancer. COX-2 makes cells resistant to apoptosis and promote angiogenesis, metastasis and cancer cell cycle by controlling number of targets. We found that, COX-2 selective inhibitors (like celecoxib and NS-398) can suppress the cancer both by COX-2 dependent and COX-2 independent pathways. COX-2 inhibitors can also produce synergic effects when used with other anti-cancer therapies. Thus, it is concluded that COX-2 selective inhibitors may be promising agents for prevention and treatment of cancer.     

选择性冠状动脉造影术中并发心室颤动的原因及防治

目的探讨选择性冠状动脉造影术（CAG）中发生心室颤动（VF）的发生率及其原因及对策。方法回顾性分析1800例冠状动脉造影术发生心室颤动病例及其原因。结果1800例（CAG）术发生Vf13例（0.09%）,VF均发生于多支血管病变,其中双支血管病变5例,3支血管病变7例,左主干病变1例。发生VF前冠状动脉压力均下降,随即发生VF。结论VF易发生于左主干及多支血管病变的患者,在CAG中要密切注意压力及心电图的变化。     

Silodosin, a novel selective alpha 1A-adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia

Silodosin is a novel selective alpha(1A)-adrenoceptor (AR) antagonist generated by Kissei Pharmaceutical Co. Ltd. This drug selectively binds to alpha(1A)-AR, which is widely distributed in the prostate, urethra and bladder trigone, involved in their contraction, located at the lower urinary tract. This high selectivity for alpha(1A)-AR contributes to inhibition of sympathetic nerve stimulation and relaxation of smooth muscle tone of the lower urinary tract tissues, resulting in suppression of increase in intraurethral pressure. Clinical data suggested that silodosin showed significant improvement in lower urinary tract symptoms associated with benign prostatic hyperplasia, as well as in quality of life. The improvements were observed in both voiding and storage symptoms. In addition, the clinical effects occurred in the early treatment phase, and were observed not only in mild cases, but also in cases with severe symptoms. Long-term study revealed that the efficacy and safety was sustained for 1 year. Although silodosin showed relatively high incidence rate of abnormal ejaculation, the adverse events associated with lowering of blood pressure were low. This article reviews preclinical and clinical data of silodosin, and introduces the usefulness of the drug for treatment of benign prostatic hyperplasia patients.     

Responses to selective D-1 and D-2 agonists after repeated treatment with selective D-1 and D-2 antagonists

This study was aimed at achieving a better understanding of the functional role of D-1 and D-2 receptors in some dopamine-mediated behaviors. Hypermotility, grooming behavior and stereotyped behavior were induced, respectively, by LY 171555 (D-2 agonist), SKF 38393 (D-1 agonist) and apomorphine (mixed agonist). Acute pretreatment either with the D-1 selective antagonist SCH 23390 (0.02 mg/kg) or with the D-2 receptor blocker YM 09151-2 (0.02 mg/kg, IP) blocked all these behaviors, suggesting the existence of functional interactions between D-1 and D-2 receptors. Striatal membranes prepared from rats receiving repeated administrations with SCH 23390 (0.05 mg/kg, twice daily for 21 days) showed an increase in the number of D-1 but not of D-2 receptors. On the contrary the repeated treatments with YM 09151-2 increased only the Bmax values of D-2 receptors. While the D-1 supersensitive rats showed only enhancement of apomorphine-induced stereotyped behavior, the D-2 supersensitive rats exhibited an increase of both apomorphine-elicited stereotypy and LY 171555-elicited hypermotility. SKF 38393-induced grooming was unaffected by any pretreatments. Moreover when D-2 supersensitive rats were acutely pretreated with SCH 23390, the enhancement of apomorphine-induced stereotyped behavior was abolished. It is concluded that the behavioral expression of D-1 receptor supersensitivity requires the simultaneous activation of D-1 and D-2 receptors.     

Sobetirome: a selective thyromimetic for the treatment of dyslipidemia

Atherosclerosis and its clinical sequelae still represent the primary cause of death in Western societies. During the past 25 years, a novel drug class to treat dyslipidemia, a main risk factor for coronary artery disease, emerged: liver- and thyroid hormone receptor isoform β-selective analogs. The present review will discuss the recent patents applied for sobetirome (GC-1), which set the course for the establishment of a novel approach to lower plasma cholesterol and triglycerides. We will focus on the major mechanisms conferring sobetirome lipid-lowering properties, including the induction of hepatic LDL receptor, the promotion of the so-called reverse cholesterol transport, and finally the induction of bile acid production and biliary sterol secretion. In summary, thyromimetics such as sobetirome may represent a useful treatment for combined hyperlipidemia, which is associated with a major cardiovascular risk.