Psychosis

Benzodiazepines or anti-psychotics, for example flupentixol, can be used in mania initially until lithium takes effect. 

Carbamazepine and valproate can be effective in bipolar depression that is unresponsive to lithium and appear to exert their action by depressing the limbic system. Both these drugs are normally used to treat epilepsy, see page 218. In bipolar depression, this is an unlicensed use. 

Psychoses are a group of disorders in which patients have a distorted perception of reality and they include reactive psychosis, paranoid/delusional psychosis, some types of mania and schizophrenia. 

Schizophrenia is the most common psychosis, affecting about 1 % of the general population. It often affects people in late adolescence and can be chronic and disabling. Schizophrenia has a number of sub-types and there have been attempts at classifying them, but this has proved difficult. Modern diagnostic classifications depend on the presence or absence of positive or negative symptoms as well as the duration of symptoms according to either the ICD-10 or the DSM-IV. 

Negative symptoms are social withdrawal, lack of emotional responsiveness and apathy positive symptoms are hallucinations (usually auditory), thought disturbances, delusions, restlessness and aggression. 

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CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

NT has been impHcated in neuroendocrine function, thermal and circadian regulation, cardiovascular and digestive system function, nociception, and in psychoses as a DA modulator. 

The hazards of chemicals are commonly detected in the workplace first, because exposure levels there are higher than in the general environment. In addition, the exposed population is well known, which allows early detection of the association between deleterious health effects and the exposure. The toxic effects of some chemicals, such as mercury compounds and soot, have been known already for centuries. Already at the end of the eighteenth century, small boys who were employed to climb up the inside of chimneys to clean them suffered from a cancer of the scrotum due to exposure to soot. This was the first occupational cancer ever identified. In the viscose industry, exposure to carbon disulfide was already known to cause psychoses among exposed workers during the nineteenth century. As late as the 1970s, vinyl chloride was found to induce angiosarcoma of the liver, a tumor that was practically unknown in ocher instances. ... 

Perhaps one of the most exciting new applications stems from the discovery in 1949 that small daily doses (l-2g) of LI2C03 taken orally provide an effective treatment for manic-depressive psychoses. The mode of action is not well understood but there appear to be no undesirable side effects. The dosage maintains the level of Li in the blood at about I mmol l and its action may be related to the influence of Li on the Na/K balance and (or) the Mg/Ca balance since Li is related chemically to both pairs of elements. 

The treatment of psychoses with enantiomers of 3- 2-[4-(6-fluoro-l,2-benzisoxazol-3-yl)-l-piperidinyl]ethyl -2-methyl-4-oxo-6,7,8,9-tetrahydro-4/f-pyrido[l,2-n]pyrimidine-9-sulfonic acid and 12 was patented (99MIP6, 99MIP7). Pamoate acid salt of 11 was prepared and patented (94MIP7). 

The most prominent pharmacologic activity exhibited by phenothiazines bearing the 1,3-propyldiamine side chain is, of course, that of a neuroleptic agent. Treatment of psychoses and severe neuroses constitutes the largest single use of these so-called... 

The efficacy of the phenothiazines for the treatment of various psychoses led to extensive synthetic programs aimed at modulation of the biologic spectrum of these molecules. As seen elsewhere, much of this work has centered on changes of the nature of the atoms that constitute the center ring. Thus, for example, it has proven possible to replace the nitrogen atom of the phenothiazine by carbon while maintaining neuroleptic activity. 

Psychoses. Major thought disorders involving distorted perception and hallucinations. 

The antianxiety drug s are contraindicated in patients with known hypersensitivity, psychoses, acute narrow-angle glaucoma, and shock. These drugp are also contraindicated in patients in a coma or with acute alcoholic intoxication with depression of vital signs. 

Warfarin is used cautiously in patients with fever, heart failure, diarrhea, malignancy, hypertension, renal or hepatic disease, psychoses, or depression. Women of childbearing age must use a reliable contraceptive to prevent pregnancy. 

Patients requiring detoxification from high or supratherapeutic dosages of benzodiazepines constitute a smaller number of patients, but they are at greater risk for life-threatening discontinuation symptoms, such as seizures, delirium, and psychoses. There has been more experience with inpatient detoxification in this group, but outpatient detoxification is possible if conducted slowly (5% reduction in dose per week), with frequent contact, and in the context of a therapeutic alliance with the patient. Often, such an alliance proves unworkable because the patient s impoverished control results in supplementation from outside sources or early exhaustion of prescribed supplies meant to be tapered. In these cases, as in the cases of patients with a history of seizures, delirium, or psychoses during previous detoxification attempts, inpatient detoxification is indicated. 

Ellinwood EH Jr Amphetamine psychoses II. theoretical implications. Int J Neuropsychiatry 4 43—54, 1968... 

Initiation of behaviour Mesolimbic pathway to nucleus accumbens from VTA (AIO) Mesocortical pathways to prefrontal cortex from VTA (AIO) Animals Increases locomotor activity and intracranial self-stimulation Humans Hallucinations, psychoses (reward, reinforcement) Animals Decreases activity and self-stimulation Humans Reduces positive symptoms of schizophrenia D2 ... 

ExCDDIs certainly improve the efficacy and duration of action of levodopa so that it can be given in a smaller dose (e.g. 25%) and generally in a 4 1 ratio, levodopa ExCDDI. As might be expected, some DA side-effects such as dyskinesia and psychoses are worse, but hypotension is less (no peripheral effects of DA) and vomiting is actually much reduced or abolished. This is because the chemoreceptor trigger zone of the vomiting centre while in the brain is on the blood side of the blood-brain barrier and will not be stimulated since no DA is formed peripherally (Fig. 15.5). That an... 

Chlorpromazine had been shown to produce a tranquil state in animals and since it had a similar effect in humans it became known as a major tranquiliser but the term is rarely used today. Sometimes the drugs used to treat schizophrenia are called anti-psychotics but more commonly neuroleptics. Leptic means to activate (take hold of) and in animals these compounds produce a state of maintained motor tone known as catalepsy. This is an extrapyramidal effect and in schizophrenics the neuroleptics can cause a number of extrapyramidal side-effects (EPSs) including Parkinsonism. The new term neuroleptic is unsatisfactory as a description of clinically useful drugs. It really describes a condition (catalepsy) seen in animals and is more indicative of a compound s ability to produce EPSs than to treat schizophrenia. Antipsychotic is more descriptive but could imply a more general efficacy in psychoses than is the case. It would seem more appropriate to call a drug that is used to treat schizophrenia an antischizophrenic just as we use the terms antidepressant or antiepileptic irrespective of how the drug works. Despite such personal reservations, the term neuroleptic will be used in this text. 

Phencyclidine (PCP), a dissociative anesthetic agent, which is subject to abuse, produces behavioral effects in man that frequently resemble schizophrenia (Luisada 1978). Manifestations of persistent psychopathology frequently remain after the acute effects of PCP have diminished. With PCP, subjects may display autistic and delusional thinking typical of schizophrenics (Luby et al. 1959). A more striking link between schizophrenia and PCP comes from observations of cases in which PCP was given to hospitalized schizophrenics (Luisada 1978). After receiving PCP, these patients showed extreme exacerbation of their psychoses the reaction persisted for up to 6 weeks. By contrast, LSD produced no more severe effects in schizophrenics than in normal subjects. 

Psychoses, when they occur, appear to be due to drug effect interacting with a vulnerable personality organization (Luisada 1978). Our experience has been that some adolescents with borderline personality disorders, as well as adolescents at risk of schizophrenic decompensation, may have this vulnerability. Although we do not have hard data to support the hypothesis that patients with PCP psychoses that are most resistant to treatment have the poorest long-term prognosis (Erard et al. 1980), our observations have been that persistence of symptoms of psychosis after the first 2 to 3 weeks of treatment often correlates with extended periods of impai rment. 

Thompson, K., Kulkarni, J. Sergejew, A. (2000). Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophr. Res., 42, 241-7. 

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