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By Q. Olivier. Muhlenberg College.

In addition buy phenergan 25 mg with amex, early studies were usually per- with Lewy bodies (DLB) also may have contributed to the formed in state hospital populations buy generic phenergan 25mg, which included pa­ apparent association between psychotic symptoms and more tients with a mixture of degenerative neurologic dementing rapid cognitive deterioration generic phenergan 25 mg fast delivery. DLB is characterized by an disorders (at least a subgroup of whom presumably had AD) early incidence and high prevalence of psychotic symptoms and patients with chronic schizophrenia who had grown old (46) purchase phenergan 25mg visa, and these patients appear to manifest a more rapidly in the institutional setting. In such early studies targeting deteriorating course of dementia (47). In a placebo-controlled study of as excessive sedation, falls, unsteady gait, and pseudoparkin­ antipsychotic drugs in a typical community nursing home sonism were more common in the active drug groups. For example, a comparison of the effects of trifluo­ placebo for reducing excitement and uncooperativeness. Al­ perazine and placebo on target symptoms of apathy, with­ though suspiciousness and hostility tended to improve more drawal, and cognitive and behavioral deterioration (loss of with active drugs than with placebo, substantial improve­ ambulation, disorientation, and incontinence) demon­ ments in these two factors also were documented in subjects strated no therapeutic effect of the active medication, and receiving placebo. One of these studies, however, is partic­ either moderate or marked improvement. Disruptive problem behaviors in­ son of the effects of thiothixene and placebo on cognitive cluded physical aggression (hitting, kicking, and pushing), deficits in a group of demented patients (55), the majority physical nonaggressive agitation (pacing and repetitive man­ of patients in both groups were rated as globally improved nerisms), and verbal aggression (screaming and cursing). Thiothixene was more effective than placebo in this 11-week, parallel-design study, but differences between groups did not become ap­ Typical Antipsychotic Drug Studies: parent until 6 weeks of treatment had been completed. The Outcome Studies since DSM-III positive effects of thiothixene appeared to persist for 3 to Since the introduction of DSM-III, a small number of pla­ 6 weeks after drug discontinuation. Taken together, these cebo-controlled studies have evaluated the efficacy of typical three studies suggest that low-dose typical antipsychotic antipsychotic drugs in patients with dementia in both out- drugs are modestly effective for treating psychotic and patient and institutional settings. Because of the use of oper­ nonpsychotic disruptive behaviors in patients with AD re- ationalized diagnostic criteria for AD and MID, one can be siding in long-term care facilities. However, parkinsonian more confident that elderly patients with chronic psychiat­ rigidity and sedation occurred in some patients in each of ric disorders beginning in early life, such as schizophrenia, these studies. In addition, the studies In a well-designed and well-executed study of the acute have clearly targeted psychotic or disruptive agitated behav­ efficacy and adverse effects of a typical antipsychotic in AD iors as outcome measures. When an a dose haloperidol and loxapine with placebo in 64 inpatients priori response criterion of at least 25% improvement in of a state psychiatric hospital (mean age, 73 years). The one of three quantifications of target symptoms was used, sample included subjects who met diagnostic criteria for response rates were significantly greater in the standard-dose either AD or MID. Both antipsychotic medications were (55% to 60%) than in either the low-dose (25% to 35%) more effective than placebo in reducing hallucinations, sus­ or placebo (25% to 35%) groups. Although effect sizes were piciousness, hostility, excitement, and uncooperativeness. Not surprisingly, moderate vored the active medications. Thirty-five percent of haloper­ to severe extrapyramidal signs developed in a subgroup of idol subjects and 32% of loxapine subjects, in comparison standard-dose haloperidol subjects (20%). Low-order but with 9% of placebo subjects, were rated as moderately or significant correlations were found between haloperidol markedly improved. Not only were therapeutic responses blood levels and symptomatic improvement, and a stronger to active drugs in these elderly demented patients lower correlation between haloperidol blood levels and extra- than would have been predicted from outcome studies in pyramidal signs. Haloperidol was effective for treating psy­ younger subjects with schizophrenia, but adverse drug ef­ chosis and agitation in AD outpatients in this study, but 1258 Neuropsychopharmacology: The Fifth Generation of Progress the therapeutic window was narrow. The authors concluded that 1 mg of risperidone peutic window in such patients may also exist for several of per day is likely to be the optimal dose for the majority the newer atypical antipsychotics (see below). In a recently of dementia patients of this age and with cognitive and reported multicenter placebo-controlled comparison of behavioral symptoms of this degree of severity. Another haloperidol, trazodone, and behavioral management for dis­ large, double-blinded, placebo-controlled trial of risperi­ ruptive agitation and psychosis in AD outpatients, haloperi­ done, haloperidol, and placebo generally supports the equiv­ dol (mean dose, 2 mg/d) was not more effective than pla­ alent efficacy of these atypical and typical antipsychotics, cebo (60). The reasons for the discrepant findings between but it also suggests an advantage of risperidone in terms of this study and the positive study reported by Devanand et extrapyramidal adverse effects (63). One possibility is tients with dementia (mean age, 81 years) were randomized that the subjects in the study of Devanand et al. Both the risperi­ placebo-controlled trial of haloperidol (53), it was in the done and haloperidol groups had significantly lower aggres­ more severely behaviorally disturbed patients that a positive sion cluster scores on the BEHAVE-AD at week 12 in com­ effect of haloperidol was detectable.

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Once the patient is in the prone position with weight applied over the pelvis order 25mg phenergan free shipping, the staff are in control of the situation buy 25 mg phenergan with visa. At some centres IMI midazolam 5mg (a benzodiazepine) and an IMI antipsychotic (haloperidol 10 mg cheap phenergan 25mg free shipping, for example) are administered simultaneously phenergan 25 mg without a prescription. The midazolam should be effective within minutes, but will be metabolized with in 2 hours. The antipsychotic will take half an hour to achieve the desired effect, but will then be effective for 6-10 hours. Until recently midazolam was administered with olanzapine, however, there were reports of this combination causing respiratory depression, and the practice has essentially ceased. Another option is to forgo the immediate benefit of midazolam and use the IMI olanzapine alone. Downward pressure (adequate but not excessive) should be maintained until there is evidence that the patient is calm and mildly sedated. This may not take as long as the pharmacology textbooks indicate, as once the medication has been given the patient may realise that further struggle is futile. If the desired effect is not obtained, oral or IMI olanzapine 10 mg can be repeated at 45 minute intervals until good control is established (to a maximum of 60 mg per day). Experience indicates that when control is difficult obtain, it is useful to regularly add a benzodiazepine to the antipsychotic, as these have different actions and there is a synergistic effect. If the patient is well known and has remained uncooperative and violent for long periods previously, the typical antipsychotic zuclopenthixol acetate (Clopixol- Acuphase) may be administered IMI at the initial “take down”. This is a calming antipsychotic which is active for about 3 days. If the patient has good insight and well organized, maintenance with an oral atypical antipsychotic is indicated. If this is not the case, a fortnightly IMI of an atypical antipsychotic may be indicated, such as risperidone 25-50 mg (Resperdal Consta). Long acting paliperidone (Xeplion) 25-50 mg need only be repeated monthly. The FGA, zuclopenthixol decanoate (200mg) is an effective alternative. An olanzapine long lasting IMI preparation (Zyprexa Relprvv) is available (210-405 mg). However, regulations about supervising patients for 3 hours post each injection is inconvenient, and some services have developed special clinics for the purpose. The period of time for which treatment continues will depend on the disorder and response to treatment. In the initial stages of schizophrenia it is best to advise that treatment will be necessary for at least 6 months, probably a year, before this question can be properly addressed. In many psychotic disorders, indefinite medication is indicated, but the patient may not accept this advice while lacking insight. Antipsychotic-induced weight gain: a review of the literature. Journal of Clinical Psychiatry 2001; 62(Suppl 7):22-31. Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approve pharmacotherapies for schizophrenia in adults. Symptom domains of schizophrenia: the role of atypical antipsychotic agents. Drug development for anxiety disorders: new roles for atypical antipsychotics. Psychopharmacology Bulletin 2004; 38 Suppl 1:38- 45. Spotlight on quetiapine in acute mania and depression associated with bipolar disorder.

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