John J. Sramek

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.

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.

Reactions to Benzodiazepines

The emergence of hostile reactions may involve increased verbal hostility and even physical assault. Often this behavior appears to be triggered by some frustrating stimulus before the patient “lashes out.” Some patients describe being very restless and pace the room before losing control.

Reactions to Antiparkinson Agents

The cardiovascular effects are dose-related. Low doses can cause transient bradycardia; moderate or high doses can cause tachycardia, palpitation, and arrhythmias (due to blockage of vagal effects on the S-A node).

Reactions to Antipsychotics

Presentation and Clinical Significance. There is decreased saliva secretion. The patient frequently complains of thirst or dry mouth.

Reactions to Lithium

Maculopapular eruptions are usually generalized and pruritic (itchy). The eruptions will clear with or without discontinuing or reducing the dosage of lithium or administering antihistamines or topical steroids.

Reactions to Antidepressants: Monoamine Oxidase Inhibitors

Hypertensive crisis usually occurs within several hours after ingestion of a contraindicated food or drug. Symptoms include occipital headaches (which may radiate frontally), sore or stiff neck, nausea, vomiting, palpitations (rapid heartbeat), fever, elevated blood pressure, sweating, photophobia (intolerance to light), and dilated pupils. Tachycardia or bradycardia may be present and can be associated with chest pain. With food reactions, factors to be considered include the amount of food eaten, the rate of gastric emptying, and the dose and potency of the monamine oxidase inhibitor (MAOI).