Typical antipsychotics treat the positive symptoms of schizophrenia (Box 21-7 Seven Categories of Positive Symptoms in Patients with Schizophrenia).
Hypotheses on Mechanism of Action
The effects of typical antipsychotics on positive symptoms have been thought to be associated with interactions with different types of dopamine receptors in the brain. The medications' interactions with one type of dopamine receptor may be associated with their antipsychotic efficacy, and those with another type may be associated with side effects such as movement disorders. However, it is now hypothesized that other neurotransmitter systems than the dopamine are also involved in psychoses.
Efficacy in Treating Symptoms
All of the typical antipsychotic agents are supposed to be equally effective. However, the amounts of the medications required to exert a certain level of antipsychotic effect vary according to their potency or the degree of interaction with different types of dopamine receptors in each individual. A high-potency agent such as haloperidol (Haldol) in a dose of 2 mg may elicit the same level of antipsychotic effect as a low-potency agent such as thioridazine (Mellaril) in a dose of 100 mg.
Long-acting agents with average half-lives of 3 weeks (Haldol decanoate) and 2 weeks (Prolixin decanoate) are available in intramuscular forms. These lipophilic agents are injected into fatty tissues in muscles of the deltoid or gluteus maximus. In the case of Haldol decanoate, a daily oral dose of 10 mg or 300 mg/month can be replaced by a monthly injection of Haldol decanoate with one third to one-half of the monthly oral dose (100 to 150 mg). The dosages for Prolixin decanoate can generally range from 12.5 to 75 mg every 2 weeks.
The low-potency typical agents have more risks of sedation and lowered seizure threshold than the high-potency agents (see Table 21-6 Potency of Typical Antipsychotics and Side Effects) in general because of the greater antagonism of cholinergic, adrenergic, and histaminergic receptor systems in the brain. However, high-potency agents have more risks for the development of extrapyramidal side effects (EPS) (Table 21-7 Signs of Extrapyramidal Side Effects) because of the potent antagonism of the dopamine receptors that are associated with movement disorders.
The other common adverse effects of antipsychotic drugs may be minimized by the considerations listed in Table 21-8 Minimizing Side Effects From the Typical and Atypical Agents.
Children
Children may be particularly vulnerable to the side effects of antipsychotics. In general, low doses of antipsychotic medications are found to be effective for many children with psychotic symptoms, autism, and vocal or motor tics.
Dosing of antipsychotics may be similar to that of adults based on the individual's body size. Side effect management becomes very important in this age group so the individual will not feel embarrassed.
Start with low doses of high-potency agents, which have less anticholinergic side effects than those with low potency. Bedtime dosing may reduce the risk of problems associated with orthostatic hypotension, such as falling. Anticholinergics that treat EPS may contribute to delirium.
Other Clinical Concerns
Psychotic Disorders Caused by Medical ConditionsPsychiatric symptoms of psychoses can be part of nonpsychiatric disorders such as Addison's disease, pernicious anemia, AIDS, CNS infection or neoplasms, Cushing's disease, delirium, dementias, lupus, and other conditions. It may be necessary to use antipsychotic medications to manage the symptoms while the underlying medical conditions are being corrected.
Reverse Epinephrine EffectCertain antipsychotics such as clozapine, fluphenazine enanthate, chlorpromazine, and thioridazine can cause epinephrine reversal and a hypotensive response when epinephrine is used to increase blood pressure.
PhotosensitivityThe skin needs to be protected from exposure to sunlight. The eyes may be more bothered by sunlight.
Heart BlockOverdoses of pimozide (Orap) or thioridazine (Mellaril) are associated with higher risk.
BlindnessHigh doses of thioridazine (Mellaril) can cause pigmentation of the retina, which could lead to blindness.