Dystonic reactions

McCarron s paper (this volume) describes the behaviors of 1,000 adults admitted to an inpatient service with acute symptoms of PCP intoxication. She states that some of the patients have appropriate behavior while many have mute and staring episodes, bizarre facial grimacing, localized dystonic reactions, rigidity, tremors, coarse jerky movements, and nystagmus. Thus, there is similarity between the acutely intoxicated adult s behavior and that of the newborn with a positive urine toxic screen for PCP. 

Side effects are increased blood pressure and heart rate, respiratory depression, apnea, muscular hypertonus, and dystonic reactions. In overdose, seizures, polyneuropathy, increased intracranial pressure, and respiratory and cardiac arrest may occur. 

A combined administration of metoclopramide and anticholinergic agent to reduce dystonic reactions of metoclopramide, did not diminish antiemetic efficacy in dogs [117], Thus, the inhibitory effect on GI smooth muscle by cholinergic blockade had no significant impact on antiemetic activity of metoclopramide. 

These compounds belong to a broad class of pharmacological agents possessing D2-dopamine blocking properties which are responsible for dystonic reactions. Prochlorperazine, the most widely used phenothiazine, was more effective than placebo but did not offer advantage over the cannabinoids or butyrophenones [123], It was less effective than metoclopramide against cisplatin [81]. 

Infrequently, SSRIs produce dystonic reactions, which are intense mnscle spasms nsnally of the face and neck. They may cause akathisia, a restless inability to sit still. Dystonic reactions and akathisia are more commonly side effects of the dopamine-blocking antipsychotics. It is believed that SSRIs prodnce these effects because increasing 5HT activity tends to decrease dopamine. When these side effects occur, the SSRI should be switched to another antidepressant. 

When an antipsychotic is needed, we prefer using one of the newer atypical agents olanzapine, ziprasidone, risperidone, quetiapine, or aripiprazole. Each of these medications reliably reduces agitation and is well tolerated. In particular, they decrease the potential for acute dystonic reactions and tardive dyskinesia caused by the typical antipsychotics. Both ziprasidone and olanzapine are now available in an injectable form that is very rapidly acting and effective in this setting. 

As you might anticipate, dopamine receptor-blocking antipsychotics lower the functional dopamine/acetylcholine ratio in the nigrostriatal pathway. As a resnlt, the antipsychotics have the same effect in this pathway as idiopathic PD. This is how antipsychotics produce their so-called extrapyramidal side effects (EPS). EPS can take the form of parkinsonism (e.g., rigidity, tremor) or acnte dystonic reactions. 

Antipsychotics also have a troublesome side effect burden that includes an often-irreversible movement disorder known as tardive dyskinesia (TD). Other side effects include so-called parkinsonism, dystonic reactions (i.e., abrupt onset of muscle spasms), akathisia (an uncomfortable sense of motoric restlessness), sedation, weight gain, dizziness, dry mouth, and constipation among others. These side effects, in particular the risk for TD, limit the usefulness of antipsychotics in the treatment of ADHD, and at this time the typical antipsychotics cannot be considered a reasonable monotherapy in uncomplicated ADHD. 

In addition to parkinsonism, another extrapyramidal side effect is the so-called acute dystonic reaction in which muscles (usually of the face or neck) go into an acute spasm. A dystonic reaction is painful and unpleasant, usually occurs early in treatment, and sometimes occurs after the very first dose of an antipsychotic. Another extrapyramidal symptom is akathisia, a restless inability to relax and sit still. Akathisia can range from a mild restlessness to extreme agitation. Rarely, patients have been known to attempt suicide during severe episodes of akathisia. It is easy to overlook akathisia, because it can easily be mistaken for a worsening of psychosis or anxiety. 

Extrapyramidal symptoms (EPS) Dystonic reactions develop primarily with the use of traditional antipsychotics. EPS has occurred during the administration of haloperidol and pimozide frequently, often during the first few days of treatment. Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, rhabdomyolysis, and acute renal failure. 

Acute dystonic reactions 1 to 2 mL IM or IV usually relieves the condition quickly. After that, 1 to 2 mL orally 2 times/day usually prevents recurrence. 

Extrapyramidal symptoms Extrapyramidal symptoms, manifested primarily as acute dystonic reactions, occur in approximately 0.2% to 1% of patients treated with the usual adult dosages of 30 to 40 mg/day. These usually are seen during the first 24 to 48 hours of treatment, occur more frequently in children and young adults, and are even more frequent at the higher doses used in prophylaxis of vomiting caused by cancer chemotherapy. If symptoms occur, they usually subside following 50 mg diphenhydramine IM. Benztropine 1 to 2 mg IM may also be used to reverse these reactions. 

Most antipsychotics and especially the piperazines and the butyrophenones can cause extrapyra-midal symptoms. Blockade of dopamine receptors mainly in the corpus striatum is held responsible for these extrapyramidal effects. They may become manifest as a variety of clinical symptoms and it should be noted that within 24 8 hours after the beginning of treatment acute dystonic reactions like torticollis, facial grimacing and opisthotonos may occur. Parkinsonism-like symptoms such as bradyki-nesia, rigidity and tremor occur after weeks or months of therapy and are more common in the elderly. Motor restlessness, i.e. akathisia, also mostly occurs not before weeks or months after starting therapy. The tendency of an antipsychotic agent to produce extrapyramidal symptoms appears to be inversely related to its ability to block cholinergic receptors. 

Intramuscular haloperidol is a suitable drug for tranquillizing violent patients, but it can be difficult to determine the correct dosage, and there is the risk of an acute dystonic reaction, particularly in younger patients. The British National Formulary recommends intramuscular injections of from 2 to 10 mg, subsequent doses being given after 4-8 hours but in exceptional cases, initial doses of up to 30 mg may be necessary. 

Acute dystonic reactions IV,IM Initially, 1-2 mg then 1-2 mg PO twice a day to prevent recurrence. 

Dystonic reactions can be managed with 50 mg diphenhydramine or 1-2 mg benz-... 

Treat acute dystonic reactions wit h parenteral diphenhydramine (2 mg/kg to max 50 mg) orbenztropine (2 mg)... 

More extrapyramidal reactions than chlorpromazine and promazine thiethylpera-zine would be less desirable than these agents in patients where the occurrence of a dystonic reaction would be hazardous (i.e., head and neck surgery patients, patients with severe pulmonary disease, patients with a history of dyskinetic reactions)... 

Extrapyramidal symptoms appear to be dose-related (particularly high doses) and are divided into 3 categories akathisia (inability to sit still, tappingof feet), parkinsonian symptoms (such as mask-like face, tremors, shuffling gait, and hypersalivation), and acute dystonias (such as torticollis, opisthotonos, and oculogyric crisis). Dystonic reactions may also produce diaphoresis and pallor. 

The most common forms of EPS that occur early in the course of treatment include acute dystonic reactions (ADRs), drug-induced Parkinsonism, and akathisia. The ADRs are involuntary muscle spasms or contractions. An ADR typically involves muscles in the neck and/or the extraocular muscles, and can be painful and... 

Campbell and co-workers conducted several controlled studies of haloperidol in autistic children (Campbell et al., 1978 Cohen et al., 1980 Anderson et al., 1984, 1989). Haloperidol, in doses of 1 to 2 mg/ day, was found to be more effective than placebo for withdrawal, stereotypy, hyperactivity, affective lability, anger, and temper outbursts. Acute dystonic reactions and withdrawal and tardive dyskinesias were not infrequent, however. 

Sleep disorders agitation, acute dystonic reactions... 

EPS include acute dystonic reactions, parkinsonian syndrome, akathisia, tardive dyskinesia, and neuroleptic mahgnant syndrome. Although high-potency conventional antipsychotics are more hkely than low-potency conventional antipsychotics to cause EPS, all first-generation antipsychotic drugs are equally hkely to cause tardive dyskinesia. The atypical antipsychotics cause suhstantially fewer EPS, which is one reason that they are recommended as first-line agents. 

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