Antipsychotic drugs extrapyramidal side-effects

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. 

Extrapyramidal side effects These are caused by antipsychotic drugs. They are characterised by motor and postural disturbances, of which the most serious is late-onset tardive dyskinesia. 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Prochlorperazine is a potent phenothiazine antipsychotic drug that is associated with a high risk of extrapyramidal side-effects, a low degree of sedation and of antimuscarinic side-effects. Chlorpromazine is less likely to induce extrapyramidal side-effects but has increased risks of inducing sedation and antimuscarinic side-effects. Olanzapine is classified as an atypical antipsychotic having characteristically much fewer incidences of extrapyramidal... 

Extrapyramidal side effects (EPS) associated with SSRI medications used as single agents were reported as early as 1979 (Meltzer et ah, 1979). Since then, several case reports have been published on use of fluoxetine (Elamilton and Opler, 1992), paroxetine (Nicholson, 1992), and sertraline (Opler 1994). The SSRI medications in combination with neuroleptics can cause severe EPS (Tate, 1989 Ketai, 1993) above and beyond what may be associated with increased levels of antipsychotic medications (Goff et ah, 1991), and are perhaps related to pharmacokinetic drug interactions. 

Antipsychotic medications, previously referred to as major tranquilizers or neuroleptics, are effective for the treatment of a variety of psychotic symptoms—such as hallucinations, delusions, and thought disorders—regardless of etiology. The term major tranquilizer is a misnomer because sedation is generally a side effect, and not the principal treatment effect. Similarly, the term neuroleptic is based on the neurological side effects characteristic of older antipsychotic drugs, such as catalepsy in animals and extrapyramidal side effects (EPS) in humans. 

Haloperidol is used as an antipsychotic and occasionally for control of acute agitation in the intensive care unit. It is can also be useful in the treatment of phencyclidine abuse. It produces a cataleptic state with little drowsiness and has minimal effects on blood pressure and respiration. It is a long-acting drug with a half-life of about 18 hours. It is available in oral and injectable preparations. In large doses extrapyramidal side effects may occur. 

One of the more serious problems occurring from the use of antipsychotics is the production of abnormal movement patterns.36,44 Many of these aberrant movements are similar to those seen in patients with lesions of the extrapyramidal system and are often referred to as extrapyramidal side effects. The basic reason that these motor problems occur is because dopamine is an important neurotransmitter in motor pathways, especially in the integration of motor function that takes place in the basal ganglia. Because antipsychotic drugs block CNS dopamine receptors, it makes sense that... 

FIGURE 8-2 Extrapyramidal side effects and their relative onset after beginning antipsychotic drug therapy. 

Tertiary-amine muscarinic receptor antagonists gain access to the central nervous system and are therefore the anticholinergic drugs used to treat parkinsonism and the extrapyramidal side effects of antipsychotic drugs. Specific agents used primarily for these conditions include benztropine mesylate (Cogentin) and trihexyphenidyl hydrochloride (Artane, others). 

Many earlier reports considered extrapyramidal side effects unavoidable when treating patients with neuroleptics. There appeared to he a parallel between antipsychotic action and the incidence of unwanted neurological effects. However, the development of newer neuroleptics has changed this view. Drugs like clozapine have a high antipsychotic potency and yet produce few neurological problems. It has therefore been proposed that the DA receptors involved in the beneficial actions of neuroleptics in the treatment of psychiatric disorders are situated in mesolimbic areas, such as the nucleus accumbens, whereas the extrapyramidal effects are mediated by striatal receptors. 

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