Pitfalls and Problems of the Long Term Use of Neuroleptic Drugs in Schizophrenia

Bristow, M. F.; Hirsch, Steven R.

doi:10.2165/00002018-199308020-00004

Cited by 13 publications

(6 citation statements)

References 62 publications

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“…Conventional antipsychotics are associated with a range of adverse events, many of which are potentially serious. These well established side-effects can be divided into neuromuscular symptoms (extrapyramidal symptoms [EPS]) and non-neuromuscular symptoms; for review, see Casey [17] and Bristow and Hirsch [12].…”

Section: Safety Of Depot Conventional Antipsychoticsmentioning

confidence: 99%

Antipsychotic agents. Gradually improving treatment from the traditional oral neuroleptics to the first atypical depot

Möller

2005

Eur. psychiatr.

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Relapse is one of the key factors in the long-term outcome of schizophrenia. The consequences of relapse are diverse and often unpredictable, and the time to recovery and degree of recovery worsen with each successive relapse. There is now overwhelming evidence that advances in antipsychotic drug treatment have led to significant reductions in the rate of relapse. This review charts the developments that have taken place in antipsychotic therapy from the introduction of depot formulations, through atypical agents, to the development of the first long-acting atypical antipsychotic. Depot formulations of conventional antipsychotics were developed in the 1960s and led to fewer relapses and episodes of hospitalization, compared with oral equivalents. Meta-analysis has confirmed that patients receiving depot antipsychotics experience significantly greater global improvement than those receiving the respective oral agents. Conventional antipsychotics are, however, associated with a range of potentially serious adverse events. The atypical antipsychotics were introduced in the 1990s and have significant advantages over conventional agents with regard to positive and negative symptoms. There is also evidence that atypical agents can reduce the risk of relapse. Importantly, atypical antipsychotics have an improved safety profile compared with older agents, particularly with regard to extrapyramidal symptoms. One disadvantage of atypical agents has been that they are only available in an oral form. The recent development of a long-acting injectable formulation of risperidone means that a new treatment option is available to physicians.

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Section: Safety Of Depot Conventional Antipsychoticsmentioning

confidence: 99%

Antipsychotic agents. Gradually improving treatment from the traditional oral neuroleptics to the first atypical depot

Möller

2005

Eur. psychiatr.

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“…Hepatic Dysfunction. Concern over the hepatic side effects of antipsychotic medications dates to early experience with an increased incidence of cholestatic jaundice from use of chlorpromazine, which may have been associated with early impurities in the drug (Bristow and Hirsch 1993). Other authors did not cite impurities as the cause of that increased incidence, but noted that chlorpromazine and other antipsychotic medications can both act as direct hepatotoxins and affect bile flow (Sherlock 1989;Leipzig 1992).…”

Section: Nonneurological Side Effectsmentioning

confidence: 99%

“…Anticholinergic side effects—dry mouth, blurred vision, constipation, confusion, temperature dysregulation—reflect activity at central and peripheral muscarinic receptors. Sedation may be a consequence of antihistaminic, central anti-alpha-adrenergic, or anticholinergic activities (Bristow and Hirsch 1993). Although newer antipsychotic medications cause fewer EPS, their activity in a variety of neurotransmitter systems may generate neuroleptic intolerance for reasons other than EPS.…”

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confidence: 99%

Neuroleptic Intolerance

Hansen

Casey

Hoffman

1997

Schizophrenia Bulletin

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This article reviews antipsychotic medication side effects, especially those that require the physician to discontinue or the patient to be noncompliant with otherwise useful medication. They include such common problems as extrapyramidal syndromes (dystonia, akathisia, drug-induced Parkinsonism, tardive dyskinesia), sedation, weight gain, and sexual dysfunction, as well as less frequent concerns, such as seizures, neuroleptic malignant syndrome, agranulocytosis, torsade de pointes, hepatitis, and dermatological and ophthalmological syndrome. The adverse events associated with some of the new antipsychotic drugs are included. Available information about individual susceptibility to side effects is addressed by syndrome.

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“…Recent research effects. Rarely, neuroleptic malignant syndrome, a potenhas investigated whether dysfunction of other neurotially fatal complication, may develop [9]. transmitters leads to abnormal dopamine function; for Many patients with schizophrenia are deemed resistant example, clozapine has affinity for many receptors, or refractory, and either gain little benefit from standard including the subtypes D 4 , 5-HT 2 and 5-HT 3 [6].…”

mentioning

confidence: 99%

The use of atypical antipsychotics in the management of schizophrenia

Campbell¹,

Young²,

Bateman³

et al. 1999

Brit J Clinical Pharma

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Long‐term drug treatment of schizophrenia with conventional antipsychotics has limitations: an estimated quarter to one third of patients are treatment‐resistant; conventional antipsychotics have only a modest impact upon negative symptoms (poverty of thought, social withdrawal and loss of affect); and adverse effects, particularly extrapyramidal symptoms (EPS). Newer, so‐called atypical, antipsychotics such as olanzapine, risperidone, sertindole and clozapine (an old drug which was re‐introduced in 1990) are claimed to address these limitations. Atypical agents are, at a minimum, at least as effective as conventional drugs such as haloperidol. They also cause substantially fewer extrapyramidal symptoms. However, some other adverse effects are more common than with conventional drugs. For example, clozapine carries a significant risk of serious blood disorders, for which special monitoring is mandatory; it also causes troublesome drowsiness and increased salivation more often than conventional agents. Some atypical agents cause more weight gain or QT prolongation than older agents. The choice of therapy is, therefore, not straightforward. At present, atypical agents represent an advance for patients with severe or intolerable EPS. Most published evidence exists to support the use of clozapine, which has also been shown to be effective in schizophrenia refractory to conventional agents. However, the need for compliance with blood count monitoring and its sedative properties make careful patient selection important. The extent of any additional direct benefit offered by atypical agents on negative symptoms is not yet clear. The lack of a depot formulation for atypical drugs may pose a significant practical problem. To date, only two double‐blind studies in which atypical agents were compared directly have been published. Neither provides compelling evidence for the choice of one agent over another. Atypical agents are many times more expensive than conventional drugs. Although drug treatment constitutes only a small proportion of the costs of managing schizophrenia, the additional annual cost of the use of atypical agents in, say, a quarter of the likely U.K. schizophrenic population would be about £56 M. There is only limited evidence of cost‐effectiveness. Atypical antipsychotics are not currently licensed for other conditions where conventional antipsychotics are commonly used, such as behaviour disturbance or dementia in the elderly. Their dose, and place in treatment in such cases have yet to be determined.

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Pitfalls and Problems of the Long Term Use of Neuroleptic Drugs in Schizophrenia

Cited by 13 publications

References 62 publications

Antipsychotic agents. Gradually improving treatment from the traditional oral neuroleptics to the first atypical depot

Antipsychotic agents. Gradually improving treatment from the traditional oral neuroleptics to the first atypical depot

Neuroleptic Intolerance

The use of atypical antipsychotics in the management of schizophrenia

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