Section 4.1

Medication-Induced Movement Disorders

Antipsychotic drugs and other drugs with dopamine-antagonist properties (for example, amoxapine) are associated with a number of uncomfortable and potentially serious neurological adverse reactions.

These adverse reactions include neuroleptic-induced parkinsonism, neuroleptic-induced acute dystonia, neuroleptic-induced tremor, neuroleptic-induced acute akathisia, neuroleptic-induced tardive dyskinesia and neuroleptic malignant syndrome.

The clinician should be aware of the symptoms of each of these adverse conditions and the treatment of each of these conditions. Patients should be fully informed of these potential adverse reactions prior to taking their medications.

Neuroleptic-Induced Parkinsonism

Description

Parkinson adverse effects occur in about 15% of patients who are treated with antipsychotic drugs, usually within 5-90 days of the initiation of the medication. The symptoms include muscle stiffness (lead pipe rigidity), cogwheel rigidity, shuffling gait, stooped posture and drooling.

The pill rolling tremor of idiopathic parkinsonism is rare but a regular, coarse tremor may be present. A focal, perioral tremor sometimes referred to as "rabbit syndrome" is another parkinsonian side effect seen with antipsychotic drugs.

Women are affected by neuroleptic-induced parkinsonism about twice as often as men. The disorder can occur at all ages, although it is most common after the age of 40. All antipsychotic drugs cause neuroleptic-induced parkinsonism, especially high-potency drugs with low anticholinergic activity.

Treatment

Neuroleptic-induced parkinsonism can be treated with anticholinergic agents, amantadine or diphenhydramine. Anticholinergics should be withdrawn after 4-6 weeks of treatment to assess whether the patient has developed tolerance to these parkinsonian effects.

Literature studies report that around 50% of patients with neuroleptic-induced parkinsonism need continued treatment with anticholinergic agents, amantadine or diphenyhydramine. These patients should be periodically assessed for their need for continued treatment.

Neuroleptic-Induced Acute Dystonia

Description

About 10% of patients experience dystonia as an adverse effect of antipsychotic drugs, usually within the first few hours of treatment. Dystonic movements can involve the neck (spasmodic torticollis or retrocollis), the jaw (forced opening resulting in dislocation of the jaw or trismus), the tongue (protrusions, twisting), and the entire body (opisthotonos).

Other dystonic reactions include oculogyric crisis (eyes turning upward and lateral), blepharospasm and glossopharyngeal dystonia, resulting in dysarthria, dysphasia and even trouble in breathing (which can cause cyanosis).

Neuroleptic-induced acute dystonias are most common in young men (less than 40 years old). However, these dystonic reactions can occur at any age in either sex. These dystonic reactions are most common with intramuscular dosages of high potency antipsychotics. But acute dystonia can occur with any antipsychotic. It is least common with thioridazine and uncommon with risperidone.

Treatment

Prophylaxis with anticholinergic or other related drugs (amantadine or diphenyhy-dramine) usually prevents the development of acute dystonia, although the risk of prophylactic treatment must be weighed against the risk of dystonia for each patient.

Treatment with IM anticholinergics or intravenous (IV) or IM diphenhydramine (50mg) almost always relieves the symptoms. Diazepam, amobarbital, caffeine with sodium benzoate and hypnosis has also been reported to be effective. In addition, the clinician may need to consider changing the antipsychotic if the neuroleptic-induced dystonia becomes problematic or repetitive.

Neuroleptic-Induced Acute Akathisia

Description

Akathisia is a subjective feeling primarily of motor restlessness that can cause the patient to be agitated, pace relentlessly, alternately sit and stand in rapid succession, and feel generally dysphoric. The symptoms can appear at any time during treatment; the symptoms are primarily motor and the symptoms cannot be controlled by the patient's will.

Treatment

With akathisia, the antipsychotic dosage should be reduced to the minimal effective level. Additional treatment for the akathisia can be attempted with anticholinergic drugs or amantadine, although these drugs are usually not effective for akathisia. Drugs that may be more effective include propanolol (30-120mg a day), benzodiazepines and clonidine.

Neuroleptic-Induced Postural Tremor

Description

Tremor is a rhythmical alteration in movement that is usually faster than one beat a second. Postural tremors decrease during periods of relaxation and often disappear in sleep. Postural tremors increase with stress and anxiety.

Antipsychotics can cause neuroleptic-induced postural tremors. But a range of psychiatric medications can also cause these postural tremors. These drugs include lithium, antidepressants and valproate.

Treatment

The treatment of postural tremors includes taking the lowest possible dose of the antipsychotic drug (or other psychiatric drug), switching the taking of the drug to bedtime (to minimize side effects during the day), and a reduction in the patient's consumption of caffeine.

If these steps prove ineffective for controlling the postural tremor, the clinician may want to consider additional treatment with a B-adrenergic receptor antagonist. For example, propanolol may be effective in these drug-induced tremors.

Neuroleptic-Induced Tardive Dyskinesia

Description

Tardive dyskinesia is a delayed effect of the antipsychotic drugs, almost always occurring after at least 6 months of treatment. The disorder consists of abnormal, involuntary, irregular choreoathetoid movements of the muscles of the head, the limbs, and the trunk. The severity of movements ranges from minimal to grossly incapacitating.

Perioral movements are the most common and include darting, twisting, and protruding movements of the tongue; chewing and lateral jaw movements; lip puckering; and facial grimacing. Finger movements and hand clenching are also common. Torticollis, retrocollis, trunk twisting, and pelvic thrusting can occur in the most severe cases.

About 10-20% of patients who are treated with antipsychotic drugs for more than a year develop tardive dyskinesia. About 15-20% of long-term hospital patients develop tardive dyskinesia. Women are more likely to be affected than men. High risk patients include patients more than 50 years of age, patients with brain damage, and patients with mood disorders.

Treatment

The three basic approaches to tardive dyskinesia are prevention, diagnosis and management. Prevention is best achieved by using the antipsychotic drugs only when clearly indicated and by using the lowest effective dosages. The new antipsychotic drug (risperidone) is associated with less tardive dyskinesia than the older antipsychotics.

Patients who are receiving antipsychotic drugs should be examined regularly (every 3-4 months) for the presence of tardive dyskinesia. The clinician should screen for the early presence of the classic buccal-lingual-masticatory syndrome. The clinician should examine the patient's tongue for vermiculiform movements or the inability to protrude the tongue for more than a few seconds.

In this tardive dyskinesia screening process, the clinician should use the Abnormal Involuntary Movement Scale (AIMS) as a guideline in the assessment of tardive dyskinesia. The clinician should record any buccal-lingual-masticatory movements, any neck or trunk movements, and any extremity movements. This evaluation should be recorded in the clinician's progress notes.

With the detection of a possible tardive dyskinesia, the clinician should also try to exclude other conditions, including stereotyped movements of schizophrenia, oral dyskinesia of advanced age, oral dyskinesia related to dental conditions, idiopathic torsion dystonia and focal dystonias (oromandibular dystonia, blepharospasm, spasmodic torticollis or ?habit spasms, tics").

Other conditions which should be excluded include Huntington?s disease, Gilles de la Tourette?s syndrome, Wilson?s disease (hepato-cerebral-lenticular degeneration due to abnormal copper metabolism), magnesium or heavy metal intoxications, Fahr?s syndrome or other disorders with calcification of the basal ganglia, post-anoxic, postencenphalitic, or encephalitic syndromes and Rheumatic (Sydenham?s) chorea (?St. Vitus? Dance?).

Other rare possibilities may include drug intoxication (L-dopa, amphetamines, less common anticholinergics, antidepressants, lithium and phenytoin), CNS complications of systemic metabolic disorders (e.g., hepatic or renal failure, hyper-thyroidism, hypoparathyroidism, hypoglycemia and vasculitis), and brain neoplasms (thalamic or basal ganglia).

Once tardive dyskinesia has been diagnosed, the clinician should consider reducing the doseage of the antipsychotic drug or even stopping. The clinician may want to consider switching the patient to clozapine or to one of the new dopamine receptor antagonists, like risperidone. Between 5-40% of all cases of tardive dyskinesia eventually remit; and between 50-90% of mild cases (if detected early) also remit.

Tardive dyskinesia has no single effective treatment. Lowering the dose of the anti-psychotic and switching to a new antipsychotic drug are the common treatment strategies. Vitamin E and high dosages of buspirone (up to 160mg a day) may be effective. Some patients (who cannot continue on any antipsychotic medication) will need to switch to other medications such as lithium, carbamazepine or the benzodiazepines - for reducing the movement disorder and the psychosis.

The clinician should document the rationale for the treatment of tardive dyskinesia and the effectiveness of that treatment. If the patient must continue on antipsychotic drugs, the clinician should re-evaluate the need for antipsychotic treatment on a regular basis (every 6 months) with clear documentation of the severity of the psychotic symptoms, the need for antipsychotic medication, and the severity of the tardive dyskinesia.

Neuroleptic Malignant Syndrome

Description

Neuroleptic malignant syndrome is a life-threatening complication that can occur at any time during the course of antipsychotic treatment. The motor and behavioral symptoms include muscular rigidity and dystonia, akinesia, mutism, obtundation and agitation. The autonomic symptoms include hyperpyrexia (up to 107 temp), sweating and increased pulse and blood pressure.

Laboratory findings with neuroleptic malignant syndrome include increased white blood cell count, creatinine phosphokinase, liver enzymes, plasma myoglobin and myoglo-binuria, occasionally associated with renal failure.

The syndrome usually evolves over 24-72 hours, and the untreated syndrome can last 10-14 days. The diagnosis is often missed early. The patient's withdrawal and agitation is often mistakenly considered to reflect increased psychosis. Men are affected more than women. Young patients are affected more than elderly patients. The mortality rate may reach 20-30% (or higher with depot medications).

Treatment

The first step in treatment is the immediate discontinuation of the antipsychotic drug, medical support to cool the patient, and monitoring of vital signs, electrolytes, fluid balance and renal output.

Dantrolene (dantrium), a skeletal muscle relaxant (at doses of 0.8-2.5mg per kg every 6 hours) may be useful in the treatment of this disorder. Once the patient can take oral medication, the dantrolene can be given in divided doses of 100-200mg per day. Bromocriptine (parlodel), at doses of 20-30mg a day, or amantadine can be added to the regimen. Treatment should continue for 5-10 days.

When antipsychotic treatment is restarted, the clinician should consider switching to a different (and low potency) antipsychotic drug. Clozapine may represent a good alternative. However, neuroleptic malignant syndrome has even been associated with clozapine treatment in some cases. This life-threatening condition can occur with any antipsychotic drug at any time.