Psychosis disorders with

Somoza EC, Winhusen TM, Bridge TP, et al An open-label pilot study of methylpheni-date in the treatment of cocaine-dependent patients with adult attention deficit/ hyperactivity disorder. J Addict Dis 23 77—92, 2004 Sora 1, Wichems C, Takahashi N, et al Cocaine reward models conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proc Natl Acad Sci U S A 95 7699-7704, 1998 Soral, Hall FS, Andrews AM, etal Molecular mechanisms of cocaine reward combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Nad Acad Sci U S A 98 5300-5305, 2001 Spear J, Alderton D Psychosis associated with prescribed dexamphetamine use 0etter). 

As would be expected, khat overuse produces symptoms similar to those of other monoamine stimulants, such as cocaine or amphetamine, including signs of sympathetic overarousal. In the extreme this can involve a toxic psychosis. Disorders more frequently associated with chronic khat use in males are headaches, anorexia, insomnia, constipation, and respiratory illnesses (Kennedy et al. 1983). Females report higher incidences of acute gastritis, jaundice, bronchitis and hepatic diseases. Also, cathinone has toxic reproductive effects in humans and experimental animals (Islam et al. 1990). It decreases sperm count and motility, and increases the number of abnormal sperm cells. It also decreases plasma testosterone in rats. 

It is well established that monotherapy with various antidepressants or mood stabilizers is relatively ineffective (i.e., they are necessary but not sufficient) for treating mood disorders with associated psychosis. Thus, psychotically depressed patients are best managed with a combination of antipsychotic-antidepressant or with electroconvulsive therapy. Although antipsychotics have a more rapid onset of action than lithium in an acute manic episode, we are unaware of clinical trials that examine the differential effect of antipsychotics or lithium for nonpsychotic versus psychotic mania. This topic is discussed further in... 

Mood Disorders. Risperidone has also been reported to benefit major depressive disorder with psychosis, bipolar mania, and schizoaffective disorder ( 83, 84, 85, 86 and 87). 

This chapter will explore the various drug treatments for psychotic disorders, with special emphasis on schizophrenia. Such treatments include not only conventional antipsychotic drugs but also the newer atypical antipsychotic drugs, which are rapidly replacing the older conventional agents. We will also take a look into the future at the drugs under development for psychosis, especially schizophrenia. Mood stabilizers for bipolar disorders were covered in Chapter 7. 

Although the usefulness of the atypical antipsychotics is best documented for the positive symptoms of schizophrenia, numerous studies are documenting the utility of these agents for the treatment of positive symptoms associated with several other disorders (discussed in Chapter 10 see Fig. 10—2). Atypical antipsychotics have become first-line acute and maintenance treatments for positive symptoms of psychosis, not only in schizophrenia but also in the acute manic and mixed manic-depressed phases of bipolar disorder in depressive psychosis and schizoaffective disorder in psychosis associated with behavioral disturbances in cognitive disorders such as Alzheimer s disease, Parkinson s disease, and other organic psychoses and in psychotic disorders in children and adolescents (Fig. 11—52, first-line treatments). In fact, current treatment standards have evolved in many countries so that atypical antipsychotics have largely replaced conventional antipsychotics for the treatment of positive psychotic symptoms except in a few specific clinical situations. 

The atypical neuroleptics—or new generation neuroleptics—cause fewer adverse side effects, are more effective in managing the symptoms of schizophrenia, and are effective for the treatment of bipolar disorder with or without psychosis. However, these drugs are cost more than the older medications. The five approved in the United States as of 2002 are ... 

The 2003 edition of The American Psychiatric Publishing Textbook of Clinical Psychiatry makes no mention of tardive psychosis or supersensitivity psychosis in the discussion of adverse neuroleptic effects, including in the section Tardive Disorders (Hales et al., 2003). Nor is there any discussion of the many studies on cognitive deficits associated with neuroleptics and in particular with TD. The only mention of tardive psychosis occurs within a discussion of mood disorders with citations to three studies spanning 1991-1993. The 1993 study points to a possible biological mechanism in the death of striatal cholinergic neurons, caused by prolonged exposure to neuroleptics (Miller et al., 1993). 

The catecholamine hypothesis of mood disorders suggests that increased DA and norepinephrine (NE) activity contribute to hyperactivity and psychosis associated with the severe stages of mania, and reduced activity causes depression. A y-aminobutyric acid (GABA) deficiency theory has been proposed for mania since it inhibits NE and DA activity. Glutamate and aspartate, excitatory amino... 

Carbamazepine and Valproic acid iiy for treatment bipolar affective disorder with psychosis... 

Drug treatment of childhood psychosis and other behavioral disorders of children is confused by diagnostic inconsistencies and a paucity of controlled trials. Antipsychotics can benefit children with disorders characterized by features that occur in adult psychoses, mania, autism, or Tourette s syndrome. Low doses of the more potent or modem atypical agents usually are preferred in an attempt to avoid interference with daytime activities or performance in school. Attention deficit disorder, with or without hyperactivity, responds poorly to antipsychotic agents, but... 

Amantadine is used cautiously in patients with seizure disorders, hepatic disease, psychosis, cardiac disease, and renal disease The antihistamines, pheno-thiazines, disopyramide, and alcohol increase the risk of adverse reactions when administered with amantadine... 

Halpern JH, Pope HG Jr Hallucinogen persisting perception disorder what do we know after 30 years Drug Alcohol Depend 69 109—119, 2003 Halpern JH, Pope HG Jr, Sherwood AR, et al Residual neuropsychological effects of illicit 3,4-methylenedioxymethamphetamine (MDMA) in individuals with minimal exposure to other drugs. Drug Alcohol Depend 7 149-152, 2004 Hatrick JA, Dewhurst K Delayed psychosis due to LSD. Lancet 2 742-744, 1970... 

Investigation of the differences in crystal packing between (431) and (426) from comparison of their respective X-ray structures, revealed that (431) was more tightly packed than (442), reflected in their respective melting points of 235 and 170 °C. It was postulated that the absence of in vivo activity for (431) may be explained by the resultant reduction in water solubility and dissolution rate compared with (426). The comparatively high calculated polar surface area of (431) (122.5A ) compared with (426) (89.3 A ) was also proposed as a factor influencing the marked difference in bioavailability between the two related compounds. Compound (426) (SLV-319) is currently being developed with Bristol-Myers Squibb for the potential treatment of obesity and other metabolic disorders. Phase I trials for obesity were started in April 2004. Earlier Phase I clinical trials for the treatment of schizophrenia and psychosis, which commenced in April 2002, appear to have been abandoned. 

An azetidine motif was also present in two series of CBi antagonist compounds disclosed by Vernalis Research [335, 336]. In the former, compound (560) was claimed to have an affinity of 285 nM in transfected HEK293 cells using tritium-labelled (382). Among the preferred indications were psychosis, schizophrenia, smoking cessation and eating disorders associated with excessive food intake. Compound (561) was claimed to have an affinity of 0.8 nM in the same binding assay [336]. 

Phencyclidine (PCP) abuse remains a serious public health problem in large urban areas of the United States, with recent trends suggesting increased use after a period of decline (Crider, this volume). Most clinical and research attention has focused on the psychiatric and medical manifestations of acute or subacute PCP intoxication, especially the organic mental disorders (toxic delirium, psychosis, or depression) that PCP can induce (McCarron et al. 1981 McCarron, this volume Sioris and Krenzelok 1978). 

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