Antipsychotic Medications Anti-psychotic Drugs pimozide, Orap

Antipsychotic: pimozide, Orap

Generic Name: pimozide
Brand Name(s): Orap
Common Use: Antipsychotic

Pimozide is a diphenylbutylpiperidine derivative with neuroleptic properties that has been found to be useful in the management of chronic schizophrenic patients. It is relatively non-sedating and can be administered in a single daily dose.

The management of the manifestations of chronic schizophrenia in which the main manifestations do not include excitement, agitation or hyperactivity. Pimozide has relatively little sedative action and can be used as a once daily medication.Pimozide is not indicated in the management of patients with mania or acute schizophrenia.

Contraindications

CNS depression, comatose states, liver disorders, renal insufficiency, blood dyscrasias, and in individuals who have previously displayed hypersensitivity to the drug. It should not be used in depressive disorders or Parkinson's syndrome.
Because pimozide prolongs the QT interval of the ECG it is contraindicated in patients with congenital long QT syndrome, patients with a history of cardiac arrhythmias, or patients taking other drugs which prolong the QT interval of the ECG.

Adverse Side Effects

Extrapyramidal symptoms consisting of akathisia, dystonia, and parkinsonism are the most commonly observed adverse effects of pimozide therapy.
The following adverse reactions have been reported with pimozide or with other antipsychotic agents:
Behavioral:
Insomnia, restlessness, agitation, drowsiness, decreased attention, fatigue and depression have been most commonly observed. Irritability, tension, jitteriness, excitement, aggressiveness, anxiety, confusion, nightmares and hallucinations have also been recorded. In some instances, aggravation of the patient's psychotic symptoms has occurred. Toxic confusional states and euphoria have been reported with other antipsychotic therapy.

Neurological:
The most commonly reported neurological adverse reactions are extrapyramidal, including parkinsonism. As with most neuroleptics, reports of parkinsonian side effects, such as tremor, rigidity and sialorrhea, are not uncommon. Akathisia occurs relatively frequently, but can usually be managed by reducing the dosage of pimozide or by the concomitant administration of an antiparkinsonian agent.

Dystonic reactions have been reported, the most common being torticollis, which is generally accompanied by oro-facial symptoms and, in some instances, oculogyric crises, as well as spasms of the face, tongue and jaw. Mouth and throat area dyskinesias, trismus, dysarthria, muscle cramps and athetoid movements have also been observed occasionally. In addition, dizziness or vertigo, weakness, excessive sweating, headache, EEG changes, and an increased incidence of epileptic seizures have been reported, and in association with other antipsychotics, opisthotonus, hyperreflexia and grand mal convulsions.

Tardive dyskinesias:
As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high-dose therapy, especially females. The symptoms are persistent and in some patients appear to be irreversible.
The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities and the trunk. There is no known effective treatment for tardive dyskinesia; antiparkinsonism agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. The physician may be able to reduce the risk of this syndrome by minimizing the unnecessary use of neuroleptics and reducing the dose or discontinuing the drug, if possible, when manifestations of this syndrome are recognized, particularly in patients over the age of 50. It has been reported that fine vermicular movements of the tongue may be an early sign of tardive dyskinesia and if the medication is stopped at that time the full syndrome may not develop.

Autonomic:
Dry mouth, blurred vision, difficulty with accommodation, urinary retention, and urinary and fecal incontinence have occurred with pimozide. Nasal congestion, paralytic ileus and reversed epinephrine effect have been reported with the use of other antipsychotics.

Cardiovascular:
Hypotension, tachycardia and fluctuations in blood pressure have been noted with pimozide. Hypertension has occasionally occurred. Changes in the ECG have also been observed and include a prolongation of the QT interval, as well as a lowering and inversion of the T wave and ST changes. Similar ECG changes have occurred in patients receiving other antipsychotic agents, notably phenothiazines. Sudden, unexpected deaths have occurred with pimozide, mainly at doses above 20 mg/day. One possible mechanism for such deaths is prolongation of the QT interval predisposing patients to ventricular arrhythmia.

Gastrointestinal:
Anorexia, nausea and/or vomiting, constipation, diarrhea, and abdominal cramps or pain have been observed in some patients receiving pimozide.

Endocrine:
Menstrual irregularities, such as amenorrhea and dysmenorrhea, and mild galactorrhea have been reported. Weight loss by patients receiving pimozide has been more commonly observed than weight gain.
Endocrine effects noted in association with the use of other antipsychotics include false positive pregnancy tests, gynecomastia, inhibition of ejaculation, mastalgia, breast engorgement, increased libido, and hyper-and hypoglycemia.

Allergic or Toxic:
Cases of urticaria and erythematous rash have been reported with pimozide, as well as instances of severe edema, generally limited to the facial area.
Fever, laryngeal edema, angioneurotic edema, asthma, anaphylactoid reactions, hyperpyrexia, obstructive jaundice, biliary stasis, photosensitivity, eczema, exfoliative dermatitis, maculopapular and acneiform reactions, and alopecia have been reported in association with the use of other antipsychotics. Blood dyscrasias (agranulocytosis, leukopenia, granulocytopenia, pancytopenia, thrombocytopenic purpura, eosinophilia, anemia, aplastic anemia) have also occurred.

Miscellaneous:
Cerebral edema, peripheral edema and altered cerebrospinal fluid proteins have been observed with other antipsychotic agents.
Since a peculiar skin-eye syndrome has been recognized as a side effect following long-term treatment with certain phenothiazines, the possibility of this side effect occurring with pimozide cannot be excluded. The reaction is marked by progressive pigmentation of areas of skin or conjunctivae and may be accompanied by discoloration of the exposed sclera and cornea. Opacities of the anterior lens and cornea described as irregular or stellate in shape have also been reported.

Neuroleptic Malignant Syndrome:
Neuroleptic malignant syndrome (NMS) has been reported with pimozide).

Hyperpyrexia:
Hyperpyrexia has been reported with other antipsychotic drugs.

Overdose

In general, the signs and symptoms of overdosage with pimozide would be an exaggeration of known pharmacologic effects and adverse reactions.

In the event of overdosage, gastric lavage, establishment of a patent airway and, if necessary, mechanically-assisted respiration are advised.

BACK TO THE LIST