Hallucinations (a false perception having no basis in reality) or delusions (false beliefs that cannot be changed with reason) are usually present. Other symptoms include disorganized speech, behavior disturbance,social withdrawal, flattened affect (absence of an emotional response to any situation or condition), and anhedonia (finding no pleasure in activities that are normally pleasurable).
Although lithium is not a true antipsychotic drug, it is considered with the antipsychotics because of its use
in regulating the severe fluctuations of the manic phase of bipolar disorder (a psychiatric disorder character
ized by severe mood swings of extreme hyperactivity to depression). During the manic phase, the person experiences altered thought processes, which can lead to bizarre delusions. The drug diminishes the frequency and intensity of hyperactive (manic) episodes.
ACTIONS
The exact mechanism of action of antipsychotic drugs is not well understood. These drugs are thought to act by inhibiting or blocking the release of the neurohormone dopamine in the brain and possibly increasing the firing of nerve cells in certain areas of the brain.These effects may be responsible for the ability of these drugs to suppress the symptoms of certain psychotic disorders. Examples of antipsychotic drugs include chlorpromazine (Thorazine), haloperidol (Haldol), and lithium. Lithium is an antimanic drug; although its exact mechanism is unknown, it appears to alter sodium transport in nerve and muscle cells and inhibits the release of norepinephrine and dopamine. Haloperidol may act to block postsynaptic dopamine receptors in the brain and depress the RAS, including those parts of the brain involved with wakefulness and emesis.
USES
Antipsychotic drugs are used to manage acute and chronic psychoses. In addition to its antipsychotic properties, chlorpromazine (Thorazine) is used to treat uncontrollable hiccoughs. Clozapine (Clozaril) is used only in patients with schizophrenia that is unresponsive to other antipsychotic drugs. Lithium is effective in the management of bipolar (manic-depressive) illness.
Some of these drugs, such as chlorpromazine (Thorazine) and prochlorperazine (Compazine), are used as antiemetics. When given in small doses, neuroleptics are effective in the control of acute agitation in the elderly
ADVERSE REACTIONS
Administration of these drugs may result in a wide variety of adverse reactions. The adverse reactions seen with the use of some of these drugs may include sedation, hypotension, postural hypotension, dry mouth,nasal congestion, photophobia (an intolerance to light), urticaria, photosensitivity (abnormal response or sensitivity when exposed to light), behavioral changes, and headache. Photosensitivity can result in severe sunburn when patients taking antipsychotic drugs are exposed to the sun or ultraviolet light.
Behavioral changes may also occur with the use of the antipsychotic drugs. These changes include an increase in the intensity of the psychotic symptoms, lethargy, hyperactivity, paranoid reactions, agitation, and confusion. A decrease in dosage may eliminate some of these symp toms, but it also may be necessary to try another drug.
Extrapyramidal Effects
Among the most significant adverse reactions associated with the antipsychotic drugs are the extrapyramidal
effects. The term extrapyramidal effects refers to a group of adverse reactions occurring on the extrapyramidal portion of the nervous system as a result of antipsychotic drugs. This part of the nervous system affects body posture and promotes smooth and uninterrupted movement of various muscle groups. Antipsychotics disturb the function of the extrapyramidal portion of the nervous system, causing abnormal muscle movement. Extrapyramidal effects include Parkinson-like symptoms, akathisia, and dystonia Extrapyramidal effects usually diminish with a reduction in the dosage of the antipsychotic drug. The primary health care provider may also prescribe an antiparkinsonism drug, such as benztropine to reduce the incidence of Parkinson-like symptoms.
Tardive Dyskinesia
Tardive dyskinesia (TD) is a syndrome consisting of potentially irreversible, involuntary dyskinetic movements. TD is characterized by rhythmic, involuntary movements of the tongue, face, mouth, or jaw and sometimes the extremities. The tongue may protrude, and there may be chewing movements, puckering of the mouth, and facial grimacing. TD may be observed in patients receiving an antipsychotic drug orafter discontinuation of antipsychotic drug therapy.
When symptoms of TD occur during the course of ther apy, use of the drug must be discontinued. Depending on the severity of the condition being treated, the primary health care provider may slowly taper the drug dose because abrupt discontinuation may result in a return of the psychotic symptoms. There is no known treatment of TD, although partial or complete remission may occur if the antipsychotic drugs are withdrawn.
The risk of TD and the likelihood that it will become irreversible increase as the duration of treatment and total cumulative dosage administered increase. It is best to use the smallest dose and the shortest duration of treatment that produces a satisfactory clinical response.
The highest incidence of TD is found in patients receiving an antiparkinson drug for extrapyramidal effects
along with an antipsychotic drug. Although any patient taking an antipsychotic can experience TD, elderly women are at highest risk.
Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome (NMS) is a rare reaction characterized by a combination of extrapyramidal effects, hyperthermia, and autonomic disturbance. It may occur hours to months after the antipsychotic drug regimen is begun. Once NMS begins, it progresses rapidly during the next 24 to 72 hours. The syndrome most often occurs in patients taking haloperidol, but has occurred with administration of thiothixene, thioridazine, and clozapine. NMS is potentially fatal and requires intensive symptomatic treatment and immediate discontinuation of use of the causative drug.
Lithium
Lithium carbonate is rapidly absorbed after oral administration. The most common adverse reactions include tremors, nausea, vomiting, thirst, and polyuria. Toxic reactions may be seen when serum lithium levels are greater than 1.5 mEq/L. Because some of these toxic reactions are potentially serious, lithium blood levels are usually obtained during therapy, and the dosage of lithium is adjusted according to the results.
CONTRAINDICATIONS
The antipsychotics are contraindicated in patients with known hypersensitivity to the drugs, in comatose patients, and in those who are severely depressed, have bone marrow depression, blood dyscrasias, Parkinson’s disease (haloperidol), liver impairment, coronary artery disease, or severe hypotension or hypertension.Antipsychotic drugs are classified as Pregnancy Category C drugs (except for clozapine, which is Pregnancy Category B). Safe use of these drugs during pregnancy and lactation has not been clearly established. They should be used only when clearly needed and when the potential good outweighs any potential harm to the fetus.
Lithium is contraindicated in patients who have hypersensitivity to tartrazine, renal or cardiovascular disease,
sodium depletion, dehydration, patients receiving diuretics, and those who are dehydrated. Lithium is a Pregnancy Category D drug and is contraindicated during pregnancy and lactation. For women of childbearing age,contraceptives may be prescribed while they are taking lithium.
PRECAUTIONS
The antipsychotic drugs are used cautiously in patients exposed to extreme heat or phosphorous insecticides and in those with respiratory disorders, glaucoma, prostatic hypertrophy, epilepsy, decreased renal function, lactation, or peptic ulcer. The antipsychotic drugs are used cautiously in elderly and debilitated patients because these patients are more sensitive to the antipsychotic drugs. Lithium is used cautiously in patients who are in situations in which they may sweat profusely and those who are suicidal, have diarrhea, or who have an infection or fever.
INTERACTIONS
Administering the antipsychotic drugs with alcohol may result in additive central nervous system (CNS) depression. Anticholinergics may reduce the therapeutic effects of the antipsychotics, causing worsening of the psychotic symptoms and an increase in the risk of tardive dyskinesia. Clozapine acts synergistically with other drugs that suppress bone marrow, resulting in an increase in the severity of bone marrow suppression. When lithium is administered with other antipsychotic drugs, lithium renal clearance may be reduced,making a decreased dosage necessary to prevent lithium toxicity. There may be a decreased effectiveness of lithium when the agent is administered with antacids.When thiazide or loop diuretics are administered with lithium, there is an increase in serum lithium levels,resulting in an increased risk for lithium toxicity.
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