Edmond H. Pi

Adverse Effects of Antipsychotic Agents

SummaryNeumleptics produce many adverse effects. While some of these are of little import beyond being a nuisance, others are both unusual and potentially serious. Since no consistent reporting mechanism has been established, the exact incidence and severity are often unclear. This article describes adverse effects of neuroleptics in general, but gives special emphasis to those areas which are most relevant at this time. ‘Unwanted’ may be preferable to ‘adverse’ as a term to describe effects which are part of the pharmacological properties of the drug but which may interfere with treatment.Unwanted effects of antipsychotic agents on the central nervous system are an important area for consideration. These include behavioural effects that present as a worsening of the condition being treated or merge with akathisia and produce distinct, recognisable abnormal behaviour that precludes improvement. Extrapyramidal syndromes are of particular importance in patients receiving treatment with antipsychotics, and in particular tardive dyskinesia which recently has gained much attention.The cardiovascular effects of neuroleptics range from hypotension to ECG changes to possible sudden death. As the elderly are more prone to almost all adverse effects, particularly of the cardiovascular and central nervous systems, extra care is recommended in geriatric patients.Endocrine changes producing sexual dysfunction and weight gain may also occur, but careful choice of an antipsychotic drug may help to minimise some of these problems in patients to whom they would be distressful. Other possible methods of diminishing unwanted effects include the measurement of plasma levels of antipsychotics, although at present well-defined therapeutic concentration ranges are not established, with the possible exception of chlorpromazine.Despite a relatively wide range of possible unwanted effects, the benefits of antipsychotic therapy are considerable; adequate knowledge of the potential adverse effects of these agents can improve their benefit to risk ratio even further.

Acute Laryngeal Dystonic Reactions to Neuroleptics

Two cases of acute laryngeal dystonia (laryngospasm), a rarely reported extrapyramidal reaction to neuroleptics, occurred in a public psychiatric hospital. A review of the literature revealed only seven well-documented case reports. This article discusses the clinical significance of this rare, alarming, and probably underreported phenomenon. Factors related to recognition, prediction, and management are also discussed. The review strongly advocates immediate intravenous administration of anticholinergic drugs to relieve dystonia.

Pharmacokinetics of desipramine in Caucasian and Asian volunteers.

The plasma levels of 20 healthy Asian subjects who received a single dose of desipramine were compared with those of 20 healthy Caucasian subjects who received such a dose. The groups differed significantly only in that Asian subjects had an earlier time of peak serum concentration.

Asian/non-Asian transcultural tricyclic antidepressant psychopharmacology: A review

1. Transcultural psychopharmacology is a discipline that seeks to determine the relative importance of society, culture, environment, genetics, and biophysiology on the prescribing and metabolism of, and response to psychotherapeutic medications. 2. Studies and surveys comparing psychotropic medication use in Asian and non-Asian populations suggest that differences may exist in drug dosage requirements, plasma drug concentrations corresponding to therapeutic and toxic effects, and the incidence and severity of adverse drug reactions. 3. This paper reviews and critiques the published controlled studies on Asian/non-Asian transcultural tricyclic antidepressant psychopharmacology, provides guidelines for the use of psychotropic medications in Asian populations, and offers suggestions for future transcultural studies. 4. Anecdotal reports suggest that differences exist between Asian and non-Asian populations in the pharmacokinetics of tricyclic antidepressants. Controlled studies have not consistently supported this view. 5. Studies with larger sample sizes and more rigorous controls are needed to determine if such differences do, in fact, exist.

Management of Tardive Dyskinesia: Current Update

SummaryTardive dyskinesia is now widely recognised as a neurological side effect produced in susceptible individuals by ingestion of neuroleptics. In general, the disorder tends to be late in onset, but has also been reported in a small number of individuals who have received neuroleptics for only brief periods. Much effort has been spent searching for predisposing factors, but the only consistent findings are that subjects are usually elderly (and elderly females in particular), in addition to having been exposed to neuroleptic agents. More recently, the increased finding of the presence of buccolingual facial movements in elderly populations never exposed to neuroleptics may bring out a re-evaluation of the role of these agents in the aetiology of tardive dyskinesia.Although much information on tardive dyskinesia has accrued in recent years, the precise definition, subtypes and pathophysiology remain unclear. With the development and availability of standardised rating scales, the clinical description of tardive dyskinesia has expanded from the initial buccolingual masticatory syndrome to include various abnormal movements of the fingers, arms, legs etc. Efforts have been made to distinguish withdrawal tardive dyskinesia from persistent tardive dyskinesia, but, irrespective of the classification, the disorder is in many instances reversible. However, it is impossible at present to predict the reversibility of each patient; therefore early detection of tardive dyskinesia remains an important clinical goal.Pharmacological treatments are based on the currently accepted hypothesis of dopamine receptor hypersensitivity. Selective dopamine blockers (D2) which suppress tardive dyskinesia without causing an increase in Parkinsonian symptoms are at various stages of development. Acetylcholine and γ-aminobutyric acid (GABA) also appear to play a reciprocal role with dopamine as seen by moderate success using cholinergics and ‘GABAergics’. However, there is no completely satisfactory treatment at present, indicating that prevention must be the primary aim. Above all, clinicians should carefully evaluate the indication for neuroleptic drugs, and avoid their use in conditions which may be treated with more benign drugs.A strategy for management of tardive dyskinesia is presented, and indications for withdrawing or continuing neuroleptics, the treatment of withdrawal dyskinesias and the role of experimental therapies are discussed.

Subjective neuroleptic response and treatment outcome under open and double-blind conditions — A preliminary report

1. A patients early subjective response to a neuroleptic was recorded in 17 schizophrenic patients following a fixed dose of neuroleptic under both open and double-blind placebo-controlled conditions. 2. High correlations were found between a patients subjective response at 2.5, 24 and 48 hours after the initial dose, suggesting that the timing of the initial subjective response rating is not critical. 3. The relationship between the psychiatric improvement and subjective response was not significant under double-blind conditions (r = 0.004), while the relationship under the open condition showed a trend towards significance comparable to earlier reports (r = 0.32). 4. The findings question the usefulness of applying early subjective response to a neuroleptic to predict clinical improvement.

Ethnicity And Medication-Induced Movement Disorders

The authors discuss the major movement disorders that can be induced by psychotropic medications and summarize what is known to date about ethnic differences in susceptibility. They discuss acute dystonias, parkinsonism, neuroleptic malignant syndrome, acute akathisia, tardive dyskinesia, and postur

Cross-cultural psychopharmacology: a review

Cross-cultural psychopharmacology seeks to determine whether there are differences in responses to psychopharmacologic agents among various ethnic groups and the reason for such variations. During the past four decades numerous clinical reports have addressed potential differences in therapeutic dosages and side effects of psychotropic medications between various ethnic groups. In addition, several rigorously designed studies have focused on ethnic differences in pharmacokinetics (including absorption, metabolism, distribution and excretion) and pharmacodynamics (including receptor-coupling activity). These ethnic variations are mainly influenced by genetic predisposition but are also influenced by other factors such as culture, environment, psychosocial supports, and attitudes towards pharmacology. This presentation will provide a critical review of the existing information in regard to psychotropic medications including neuroleptics, antidepressants, lithium, and benzodiazepines among various ethnic groups. Also included will be data on neuroleptic-induced movement disorders, the clinical implications of genetic polymorphism of cytochrome P-450 isoenzymes, recommendations on how to better design a pharmacological approach in the treatment of psychiatric disorders among different ethnic groups, as well as recent advances and future directions regarding cross-cultural issues of psychopharmacology.

Relationship between plasma desipramine levels and clinical outcome for RDC major depressive inpatients

Depressed patients (N=31), who met Research Diagnostic Criteria for major affective disorder-depressed, were severely ill and maintained drug-free for a 1-week period on inpatient status. They received a fixed dose (150 mg/day) of desipramine for a 4-week period with drug plasma level determination and clinical ratings performed at fixed time intervals throughout the study. Despite these rigid criteria for entrance and clinical outcome measures, no obvious relationship between plasma desipramine level and clinical outcome was found. The clinical implications of this finding are discused.

Issues in Pharmacological Treatment

The history of psychopharmacology is only three and a half decades old, dating back to the discovery of the first neuroleptic (chlorpromazine) in the early 1950s. This discovery may be considered one of the major advances in twentieth-century medicine. Like most advances, the introduction of chlorpromazine led to a period of rapidly expanding use, if not overuse, followed by a more gradual delineation of the specific areas of the drug’s usefulness.