Section 3.5.1

Amantadine

General Description

Amantadine (Symadine, Symmetrel) is a dopamine agonist that is used primarily for the treatment of medication-induced movement disorders, such as neuroleptic induced parkinsonism.

Indications for Medication

The primary indication for amantadine in psychiatry is for the treatment of extra-pyramidal signs and symptoms, such as parkinsonism, akinesia and so called rabbit syndrome (focal perioral tremor of the choreoathetoid type) caused by the administration of antipsychotic drugs.

Amantadine is as effective as the anticholinergic drugs for treatment of the extra-pyramidal signs and symptoms; and it results in improvement in approximately one half of all patients. Amantadine, however, is not generally considered as effective as the anticholinergics for the treatment of acute dystonic reactions.

Amantadine may be the drug of choice when the clinician does not want to add an additional anticholinergic drug to an antipsychotic medication regimen. This may be particularly true if the patient is taking antipsychotic drugs with high anticholinergic effects or if the patient is elderly with the increased sensitivity to anticholinergic activity.

Clinical Guidelines

Amantadine is usually started at a dose of 100mg given orally twice a day, although the dose may be increased up to 300mg, given in divided doses.

If amantadine is successful in the treatment of drug-induced extrapyramidal symptoms, consideration should be given for continuing it for four to six weeks, then discontinuing it to see if the patient has become tolerant to the neurologic side effects of the antipsychotic medication.

If amantadine is no longer necessary, it should be tapered over one to two weeks. If it is necessary, it should be maintained at the lowest possible dose.

Adverse Effects

The most common CNS effects are mild dizziness, insomnia and impaired concentration (dose related) which occurs in 5-10% of all patients. Irritability, depression, anxiety, dysarthria and ataxia (tremor and hyperexcitability) occur in 1-5% of patients; hallucinations may also occur.

Amantadine is relatively contraindicated in patients with renal disease or a seizure disorder. Amantadine should be used with caution in patients with edema or cardiovascular disease.

Some evidence indicates that amantadine is teratogenic and it should not be used in pregnant women. Because amantadine is excreted in milk, women who are breast-feeding should not be given the drug.

Drug-Drug Interactions

The co-administration of amantadine with CNS stimulants can result in insomnia, irritability, nervousness and possibly seizures or irregular heartbeat. Amantadine should not be co-administered with anticholinergics because of the potential increase in unwanted side effects such as confusion, hallucinations, nightmares, dryness of mouth and blurred vision.

The consent form for these medications is "Side-Effect Medication (Anticholinergic)".

Anticholinergics

General Description

Anticholinergic drugs are used in psychiatry for the treatment of medication-induced movement disorders, such as neuroleptic-induced parkinsonism. Six anticholinergic drugs are available in the United States. The variations among the six drugs are of little significance except for local differences in cost. The two most commonly used anticholinergic drugs are benztropine (Cogentin) and trihexyphenidyl (Artane).

Indications for Medication

The anticholinergic drugs are effective in the treatment of neuroleptic-induced acute dystonia reactions, neuroleptic-induced parkinsonism (including rabbit syndrome), and the neuroleptic-induced akathisia. The anticholinergics are less effective for the treatment of akathisia which is perhaps better treated with B-adrenergic receptor antagonists (propranolol), benzodiazepines (lorazepam), or a reduction of the dose of the antipsychotic medication.

Clinical Guidelines

For the treatment of acute dystonic reactions, benzotropine 1-2mg IM should be administered. If the drug is not effective in 20-30 minutes, a second dose of the drug should be administered. If the patient still does not respond, a benzodiazepine or an antihistamine may be necessary.

For treatment of chronic drug-induced extrapyramidal symptoms, anticholinergic drugs should be administered 1-4 times daily. A typical dose would be 1-2mg of benzotropine (or its equivalent drug) twice daily.

If the anticholinergic drugs are successful in the treatment of drug-induced extrapyramidal symptoms, consideration should be given to discontinuing them after four to eight weeks to see if the patient needs the medication.

If the anticholinergic drugs are no longer necessary, they may need to be tapered over one to two weeks. If they are necessary, they should be maintained at the lowest possible dose.

Clinicians in favor of prophylaxis argue that the use of anticholinergic drugs improves compliance and decreases recidivism. Clinicians opposed to prophylactic treatment with anticholinergic drugs cite the increased risk of anticholinergic toxicity and tardive dyskinesia. Most clinicians agree on some prophylactic treatment in the patients who are at the higher risk for acute dystonic reactions: young adult males.

Adverse Effects

Anticholinergic drugs should be given cautiously, if at all, to patients with prostatic hypertrophy, urinary retention, narrow-angle glaucoma, cardiovascular disease or myasthenia gravis.

Anticholinergic drugs should be used with caution in patients with hepatic or renal disease because the anticholinergic activity exacerbates those medical problems.

Use of anticholinergics in the elderly should be minimized when possible due to the risk of cognitive impairment.

The anticholinergic drugs are occasionally used as drugs of abuse on the street because of their mild mood-elevating properties. Abuse may lead to anticholinergic toxicity. Symptoms of anticholinergic toxicity can include delirium, coma, seizures, extreme agitation, hallucinations, severe hypotension, supraventricular tachycardia and the usual peripheral manifestations - flushing, mydriasis, dry skin, hyperthermia and decreased bowel sounds.

Anticholinergic drugs have not been studied in pregnancy. They have not been reported to cause problems in nursing babies. However, they should be used with caution in pregnant women or nursing mothers.

Drug-Drug Interactions

The most common drug-drug interactions with the anticholinergic drugs occur when they are co-administered with psychotropics that also produce high anticholinergic activity. These drugs would include many antipsychotics, tricyclic and tetracyclic antidepressants, and monoamine oxidase inhibitors.Many over the counter cold preparations also produce significant anticholinergic activity. The co-administration of these drugs with anticholinergic drugs may cause anticholinergic intoxication. Anticholinergic drugs may have addictive effects with CNS depressants, including alcohol.

The consent form for these medications is "Side-Effect Medication (Anticholinergic)".

Antihistamines

General Description

Antihistamines are used in psychiatry primarily for the treatment of drug-induced extrapyramidal symptoms and as mild hypnotics and sedatives. Diphenhydramine (Benadryl) is used for the treatment of extrapyramidal symptoms and sometimes as a hypnotic; and hydroxyzine hydrochloride (Atarax) and hydroxyzine pamoate (Vistaril) are used as sedatives.

Indications for Medication

The use of antihistamines for medication-induced movement disorders is a possible alternative to anticholinergics and amantadine (Symadine, Symmetrel), especially in patients who are especially sensitive to anticholinergic effects and who cannot tolerate amantadine.

The antihistamines are relatively safe hypnotics, although they are not superior to the benzodiazepines. The antihistamines have not been effective as anxiolytic therapy for more than a few months. The benzodiazepines and buspirone (Buspar) are more effective for chronic anxiolytic therapy.

Clinical Guidelines

Diphenhydramine is used in the short-term and long-term treatment of drug-induced extrapyramidal symptoms and as a hypnotic. The typical dose range of diphenhydramine is from 50-200mg daily. If diphenhydramine is used in the injectable IM form, the injections should be given deep since superficial injections cause local irritation.

Hydroxyzine is most commonly used as a short-term anxiolytic. For short-term treatment, hydroxyzine may be administered IM (never IV), 50-100mg, every four to six hours. For longer treatment, hydroxyzine is usually given 50-400mg daily in the treatment of anxiety.

Adverse Effects

Antihistamines are commonly associated with sedation, dizziness and hypotension, all of which can be severe in elderly patients. Poor motor coordination can result in accidents. Other common adverse effects include epigastric distress, nausea, vomiting, diarrhea and constipation.

Antihistamines should be used with caution in patients with urinary problems, asthma, enlarged prostate or glaucoma. Diphenhydramine should be used in pregnancy only if clearly needed. Hydroxyzine is contraindicated in early pregnancy because of reports of fetal damage in animals.

Drug-Drug Interactions

The sedative property of antihistamines can be additive with central nervous system CNS depressants, including alcohol, other sedative-hypnotic drugs, and psychotropic drugs. The anticholinergic activity of antihistamines can be additive with other drugs, causing increased anticholinergic symptoms.

A word of caution: antihistamines compounded with decongestants should not be taken within two weeks of a MAOI. Co-administration of antihistamines with opioids can increase the rush experienced by addicts. Therefore, a potential for abuse of antihistamines is associated with this group of patients.

The consent form for these medications is "Side-Effect Medication (Anticholinergic)."