eMedicine Specialties > Emergency Medicine > Toxicology
Toxicity, Neuroleptic Agents: Treatment & Medication
Updated: Sep 15, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Be aware that patients with major tranquilizer overdose are at risk of rapid deterioration with coma, seizures, hypotension, or dysrhythmias. They all require transport to a hospital facility because the severity of overdose cannot be ascertained immediately after ingestion.
- Prehospital treatment with activated charcoal, 1 g/kg, is indicated as soon as possible. This can be administered in the field if permitted by local protocol.
- Establish a large-bore IV line of isotonic sodium chloride solution in anticipation of possible hypotension or the need to administer medications.
- Seizure activity usually responds to diazepam in the usual anticonvulsant doses.
- Treat ventricular dysrhythmias with standard advanced cardiac life support (ACLS) pharmaceutical agents.
Emergency Department Care
ED care varies, depending on the patient's condition and on the care already provided in the field.
- No specific antidote for any of the major tranquilizers exists.
- The standard approach to resuscitation (airway, breathing, circulation, drugs, and environment [ABCDE]) is employed as indicated by the patient's condition. Active airway management is indicated for patients who are in shock, status epilepticus, coma, or cardiac arrest.
- Placement of a Foley catheter may be necessary in comatose patients or those with shock or severe dehydration to monitor urine output and to obtain urine specimens in patients who may have urinary retention from the anticholinergic effects of the overdose.
- Activated charcoal
- If used within 2 hours of ingestion, gastric lavage may be useful in decreasing the absorption of major tranquilizers. Protect the patient's airway before lavage if an altered level of consciousness is present. Many toxicologists now advise against lavage and recommend administering activated charcoal orally or by nasogastric tube.
- Activated charcoal with a saline cathartic remains the GI decontamination method of choice. Major tranquilizers are generally well bound by activated charcoal and should be administered in standard doses as soon as possible postingestion.
- Multiple dose activated charcoal is of limited benefit and cannot be used if an ileus is present.
- Ipecac syrup is never recommended.
- Hemoperfusion, hemodialysis, and forced diuresis are not effective.
- Seizures are treated in a step-wise fashion, beginning with benzodiazepines (eg, diazepam, lorazepam) and followed by barbiturates (eg, phenobarbital, pentobarbital).
- The combination of peripheral alpha-blockade and dehydration may result in severe hypotension during major tranquilizer overdose. Initial treatment involves administration of a volume challenge with isotonic sodium chloride solution. If the patient remains hypotensive after fluid challenge or manifests signs of cardiogenic shock, pressor agents may be required.
- Norepinephrine is the preferred pressor agent in this circumstance because it has pure alpha-agonist effects.
- Paradoxically, epinephrine or dopamine may lower the blood pressure because alpha-blockade from major tranquilizer causes unopposed beta-agonist peripheral vasodilation.
- For patients manifesting NMS with worsening hyperthermia, immediate cooling measures, such as fans, wet cloths, ice packs in groin and axilla, and rectal acetaminophen, are indicated.
- Dantrolene sodium (1-10 mg/kg) is recommended as adjunctive therapy for patients manifesting severe hyperthermia (rectal temperatures >105°F) and muscle rigidity.
- Dantrolene is incompatible with acidic solutions and is mixed with sterile water for injection. It must be given directly by slow IV push or by intravenous piggyback into a large-bore IV near the needle with the IV fluid shut off. Great care must be taken to avoid extravasation into the tissues.
- Dantrolene is given by 1-2 mg/kg doses until a maximum dose of 10 mg/kg or until the rectal temperature breaks.
- Dantrolene may be effective in malignant hyperthermia by acting in dissociating the excitation-contraction coupling of skeletal muscles. While the precise mechanism of action and molecular targets are still incompletely known, dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. In the April 2004 issue of Anesthesia, Krause et al stated that recent studies have identified the ryanodine receptor (the major calcium release channel of the skeletal muscle sarcoplasmic reticulum) as a dantrolene-binding site.5 A direct or indirect inhibition of the ryanodine receptor is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene acts primarily peripherally and has no effect on the cardiovascular or respiratory systems in this acute setting.
- Recent studies have questioned the efficacy of dantrolene6 , but anecdotal reports still advocate for its use. Dantrolene should not be used as monotherapy.
- Bromocriptine and amantadine are central dopaminergic agonists that may be effective in reversing the dopaminergic blockade caused by the neuroleptics. They have been reported as effective in treating NMS but work slowly (eg, over several days). They are given orally or by nasogastric tube.
- Oral levodopa, with or without carbidopa, and intravenous levodopa are therapies used more commonly in patients with Parkinson disease who develop NMS on sudden withdrawal of their dopaminergic therapy. Steroid pulse therapy is also useful in NMS for reducing the illness duration and improving symptoms in patients with Parkinson disease.
Consultations
- Notification of the regional poison control center is indicated.
- In complex or severe cases, consult with the regional poison control center or a medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine) for additional information and patient care recommendations.
- A psychiatric assessment is indicated once the patient's medical condition has stabilized to determine any suicidal intent.
Medication
No specific antidotes exist for the adverse effects of neuroleptic medications. Because these effects are so diverse and do not occur in most cases, prophylactic treatment for seizures, dystonia, dysrhythmias, or NMS is not indicated.
GI decontaminants
Empirically used to minimize systemic absorption of the toxin. May only be of benefit if administered within 1-2 h of ingestion.
Activated charcoal (Liqui-Char)
Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
For maximum effect, administer within 30 min of ingesting poison.
Generally mixed and administered with a saline cathartic (do not use sorbitol).
Adult
1 g/kg (50-100 g) PO
Pediatric
1-2 g/kg (15-30 g) PO
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases adsorptive properties)
Documented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway with absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for presence of bowel sounds to minimize risk of charcoal ileus; not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before giving activated charcoal; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black
Anticonvulsants
Indicated for seizures and status epilepticus associated with major tranquilizer overdose. Compared to lorazepam, advantages of diazepam are more rapid onset of action and decreased cost. The disadvantage is that diazepam has a brief duration of anticonvulsant activity (20 min) compared to lorazepam (several hours). Both drugs can aggravate hypotension, which may limit their usefulness in this setting.
Barbiturates are usually not necessary in neuroleptic overdose because most patients respond to benzodiazepines. Phenobarbital is the most commonly used anticonvulsant, but shorter-acting barbiturates are also effective.
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Seizures are relatively common in association with major tranquilizer overdose because most neuroleptics lower seizure threshold. In the ED, standard protocol is used for terminating seizures.
Adult
5-10 mg IV
Pediatric
30 days to 5 years: 0.2-0.3 mg IV slowly; may repeat q5min X 2
Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity); monitor for respiratory depression and hypotension with high or repeated doses
Lorazepam (Ativan)
Sedative hypnotic with short onset of effects and relatively long half-life.
By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.
Monitoring blood pressure after administering dose is important. Adjust prn.
Adult
0.5-2 mg IV slowly; titrate to effect
Pediatric
Infants and children: 0.1 mg/kg IV slowly; may repeat q5min X 2
Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs
Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease; monitor for respiratory depression with high or repeated doses; contains benzyl alcohol, which may be toxic to infants in high doses
Phenobarbital (Barbita, Luminal)
Interferes with transmission of impulses from thalamus to cortex of brain. Effective in terminating convulsions, but use is often limited by hypotension associated with neuroleptic overdose.
Adult
15-20 mg/kg IV slowly; not to exceed 1 g
Pediatric
15-20 mg/kg IV slowly
May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and fatality; chloramphenicol, valproic acid, and MAOIs may increase phenobarbital toxicity; rifampin may decrease phenobarbital effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy); menstrual irregularities also may occur
Documented hypersensitivity; severe respiratory disease, marked impairment of liver function, and nephritic patients
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access
Adult
0.01-0.05 mg/kg IV (usually 0.5-4 mg)
Pediatric
<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg followed by continuous infusion of 1 mcg/kg/min, titrating dose upward q5min until seizures controlled
Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when using together
Documented hypersensitivity; preexisting hypotension, narrow-angle glaucoma, and sensitivity to propylene glycol (diluent)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages in organic brain syndrome and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Cardiovascular agents
Use of direct-acting alpha-agonists is preferred when hypotension persists after adequate volume challenge with isotonic sodium chloride solution IV. Pressors with actions at beta- and alpha-receptors (eg, dopamine, epinephrine) may exert only a beta (vasodilatory) effect in the face of neuroleptic-induced alpha blockade; consequently, a paradoxical drop in blood pressure may occur if the pressors are used.
Dysrhythmias are relatively common in neuroleptic overdose. Prolongation of the QT interval may result in torsade de pointes. The quinidinelike effect on the slope of phase 0 of the ECG may result in widening of the QRS. Magnesium may be an effective treatment.
Norepinephrine (Levophed)
Stimulates beta1- and alpha-adrenergic receptors, which, in turn, increases cardiac muscle contractility, heart rate, and vasoconstriction. As a result, systemic blood pressure and coronary blood-flow increases.
Adult
0.5-1.0 mcg/min (usually 2-12 mcg/min) IV; titrate to effect
Pediatric
0.1 mcg/kg/min IV; carefully titrate to effect
Atropine enhances the pressor response by blocking the reflex bradycardia caused by norepinephrine
Documented hypersensitivity; peripheral or mesenteric vascular thrombosis because ischemia may be increased and area of infarct extended
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Correct blood-volume depletion, if possible, before giving norepinephrine therapy; extravasation may cause severe tissue necrosis and, thus, should be administered into a large vein; caution in occlusive vascular disease; monitor for cardiac ischemia and dysrhythmias
Magnesium sulfate
Currently DOC for treatment of torsade de pointes and may be an effective antiarrhythmic for ventricular and supraventricular tachycardia.
Adult
Step 1: 2 g IV bolus over 3-5 min
Step 2: Repeat 2 g IV bolus if partial response in 15 min but monitor for hypotension
Step 3: Pacing or isoproterenol if torsade de pointes continue
Pediatric
0.2-0.4 mEq/kg (25-50 mg/kg) IV slowly
Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade observed with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine
Documented hypersensitivity; heart block, Addison disease, myocardial damage, hypermagnesemia, renal failure, or severe hepatitis
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
May alter cardiac conduction leading to heart block in digitalized patients; monitor respiratory rate, deep tendon reflex, and renal function when electrolyte is administered parenterally; caution when administering because may produce significant hypertension or asystole; in overdose, calcium gluconate (10-20 mL IV of 10% solution) can be administered as antidote for clinically significant hypermagnesemia
Skeletal Muscle Relaxant
Dantrolene is currently recommended as treatment for hyperthermia associated with neuroleptic malignant syndrome. Acts to restore calcium entry into muscle sarcoplasmic reticulum, causing muscle relaxation and decreasing heat production from muscle.
Dantrolene (Dantrium)
Stimulates muscle relaxation by modulating skeletal muscle contractions at site beyond myoneural junction and acting directly on muscle itself. Doses may be repeated, not to exceed 10 mg/kg.
Adult
1 mg/kg through large-bore IV carefully with IV fluids shut off; avoid extravasation; see dosing and technique above
Pediatric
Administer as in adults
Toxicity may increase with the coadministration of clofibrate and warfarin; coadministration with estrogen may increase hepatotoxicity in women >35 y; concurrent use with verapamil can lead to hyperkalemia and myocardial depression
Documented hypersensitivity; active hepatic disease (hepatitis, cirrhosis)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause hepatotoxicity (use only for recommended indications); caution in impaired pulmonary function and severe cardiac insufficiency; may cause photosensitivity with exposure to sunlight
Antihistamines
Agents with anticholinergic properties are effective in terminating acute dystonias associated with neuroleptic use.
Diphenhydramine (Benadryl)
Anticholinergic medications help restore balance between dopaminergic and cholinergic neurotransmission. Dopaminergic transmission is decreased by neuroleptic drugs.
Adult
1 mg/kg IV; up to 50 mg
Pediatric
Administer as in adults
Potentiates effect of CNS depressants; because of alcohol content, do not give syrup dosage form to patients taking medications that can cause disulfiramlike reactions
Documented hypersensitivity; MAOIs; hyperthermia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction
Dopamine agonist
Can reverse the dopamine blockade caused by neuroleptics and has been reported to be useful in reversing NMS symptoms.
Bromocriptine (Parlodel)
Semisynthetic ergot alkaloid derivative. Strong D2-receptor agonist, partial D1-receptor agonist. Stimulates dopamine receptors in corpus striatum.
Approximately 28% absorbed from the GI tract and metabolized in the liver. Approximate elimination half-life is 50 h with 85% excreted in feces and 3-6% eliminated in urine.
Adult
2.5-5 mg PO or NG tube bid
Pediatric
Not established
Toxicity may increase with ergot alkaloids and isometheptene; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease bromocriptine effects
Documented hypersensitivity; ischemic heart disease, peripheral vascular disorders
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic disease; suppresses lactation and should not be given to breastfeeding women
Amantadine (Symmetrel)
Inhibits N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine release in rat striatum. May enhance dopamine release, inhibit dopamine reuptake, stimulate postsynaptic dopamine receptors, or enhance dopamine receptor sensitivity.
Adult
100 mg PO or NG tube bid
Pediatric
Not established
Drugs with anticholinergic or CNS stimulant activity increase amantadine toxicity; the concurrent administration of hydrochlorothiazide plus triamterene with amantadine may increase plasma concentrations of amantadine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in liver disease, uncontrolled psychosis, eczematoid dermatitis, seizures, and in those receiving CNS stimulant drugs; reduce dose in renal disease when treating Parkinson disease; do not discontinue this medication abruptly
More on Toxicity, Neuroleptic Agents |
| Overview: Toxicity, Neuroleptic Agents |
| Differential Diagnoses & Workup: Toxicity, Neuroleptic Agents |
 Treatment & Medication: Toxicity, Neuroleptic Agents |
| Follow-up: Toxicity, Neuroleptic Agents |
| References |
| « Previous Page | Next Page » |
References
DeSilva P, Fenton M, Rathbone J. Zotepine for schizophrenia. Cochrane Database Syst Rev. Oct 18 2006;CD001948. [Medline].
Haddad PM, Serdar M. Neurological complications of psychiatric dugs:clinical features and management. Human Psychopharmacology. Jan 2008;23 Suppl 1:15-26. [Medline].
DE Hert M, Schreurs V, Vancampfort D, VAN Winkel R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry. Feb 2009;8(1):15-22. [Medline].
Shirzadi AA, Ghaemi SN. Side effects of atypical antipsychotics: extrapyramidal symptoms and the metabolic syndrome. Harv Rev Psychiatry. May-Jun 2006;14(3):152-64. [Medline].
Krause T, Gerbershagen MU, Fiege M, et al. Dantrolene--a review of its pharmacology, therapeutic use and new developments. Anaesthesia. Apr 2004;59(4):364-73. [Medline].
Reulbach U, Dutsch C, Biermann T, Sperling W, Thuerauf N, Kornhuber J, et al. Managing an effective treatment for neuroleptic malignant syndrome. Crit Care. 2007;11(1):R4. [Medline].
Ananth J, Parameswaran S, Gunatilake S. Side effects of atypical antipsychotic drugs. Curr Pharm Des. 2004;10(18):2219-29. [Medline].
Ananth J, Parameswaran S, Gunatilake S, et al. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry. Apr 2004;65(4):464-70. [Medline].
Bhanushali MJ, Tuite PJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurol Clin. May 2004;22(2):389-411. [Medline].
Brady WA. Life threatening syndromes presenting with altered mentation and muscular rigidity. Emerg Med Rep. 1999;20:5160.
Capel MM, Colbridge MG, Henry JA. Overdose profiles of new antipsychotic agents. Int J Neuropsychopharmacol. Mar 2000;3(1):51-54. [Medline].
Carbone JR. The neuroleptic malignant and serotonin syndromes. Emerg Med Clin North Am. May 2000;18(2):317-25, x. [Medline].
Correll CU, Penzner JB, Parikh UH, Mughal T, Javed T, Carbon M. Recognizing and monitoring adverse events of second-generation antipsychotics in children and adolescents. Child Adolesc Psychiatr Clin N Am. Jan 2006;15(1):177-206. [Medline].
Dubois D. Toxicology and overdose of atypical antipsychotic medications in children: does newer necessarily mean safer?. Curr Opin Pediatr. Apr 2005;17(2):227-33. [Medline].
Ener RA, Meglathery SB, Van Decker WA, Gallagher RM. Serotonin syndrome and other serotonergic disorders. Pain Med. Mar 2003;4(1):63-74. [Medline].
Ferrando SJ, Eisendrath SJ. Adverse neuropsychiatric effects of dopamine antagonist medications. Misdiagnosis in the medical setting. Psychosomatics. 1991;32(4):426-32. [Medline].
Fleishman SB, Lavin MR, Sattler M, Szarka H. Antiemetic-induced akathisia in cancer patients receiving chemotherapy. Am J Psychiatry. May 1994;151(5):763-5. [Medline].
Gareri P, De Fazio P, De Fazio S, Marigliano N, Ferreri Ibbadu G, De Sarro G. Adverse effects of atypical antipsychotics in the elderly: a review. Drugs Aging. 2006;23(12):937-56. [Medline].
Gil-ad I, Shtaif B, Shiloh R, Weizman A. Evaluation of the neurotoxic activity of typical and atypical neuroleptics: relevance to iatrogenic extrapyramidal symptoms. Cell Mol Neurobiol. Dec 2001;21(6):705-16. [Medline].
Hasan S, Buckley P. Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique. Am J Psychiatry. Aug 1998;155(8):1113-6. [Medline].
Haupt DW. Differential metabolic effects of antipsychotic treatments. Eur Neuropsychopharmacol. Sep 2006;16 Suppl 3:S149-55. [Medline].
Heiman-Patterson TD. Neuroleptic malignant syndrome and malignant hyperthermia. Important issues for the medical consultant. Med Clin North Am. Mar 1993;77(2):477-92. [Medline].
Herrmann N, Lanctot KL. Do atypical antipsychotics cause stroke?. CNS Drugs. 2005;19(2):91-103. [Medline].
Isbister GK, Balit CR, Kilham HA. Antipsychotic poisoning in young children: a systematic review. Drug Saf. 2005;28(11):1029-44. [Medline].
Knight ME, Roberts RJ. Phenothiazine and butyrophenone intoxication in children. Pediatr Clin North Am. Apr 1986;33(2):299-309. [Medline].
Le Blaye I, Donatini B, Hall M. Acute overdosage with clozapine: A review of the available clinical experience. Pharm Med. 1992;6:169.
Le Blaye I, Donatini B, Hall M, Krupp P. Acute overdosage with thioridazine: a review of the available clinical exposure. Vet Hum Toxicol. Apr 1993;35(2):147-50. [Medline].
Lee SH, Yang YY. Reversible neurotoxicity induced by a combination of clozapine and lithium: a case report. Zhonghua Yi Xue Za Zhi (Taipei). Mar 1999;62(3):184-7. [Medline].
Love JN, Smith JA, Simmons R. Are one or two dangerous? Phenothiazine exposure in toddlers. J Emerg Med. Jul 2006;31(1):53-9. [Medline].
McCarron MM, Boettger ML, Peck JJ. A case of neuroleptic malignant syndrome successfully treated with amantadine. J Clin Psychiatry. Sep 1982;43(9):381-2. [Medline].
Newcomer JW, Haupt DW. The metabolic effects of antipsychotic medications. Can J Psychiatry. Jul 2006;51(8):480-91. [Medline].
Nicholson D, Chiu W. Neuroleptic malignant syndrome. Geriatrics. Aug 2004;59(8):36, 38-40. [Medline].
Pacher P, Kecskemeti V. Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?. Curr Pharm Des. 2004;10(20):2463-75. [Medline].
Pelonero AL, Levenson JL, Pandurangi AK. Neuroleptic malignant syndrome: a review. Psychiatr Serv. Sep 1998;49(9):1163-72. [Medline].
Pierre JM. Extrapyramidal symptoms with atypical antipsychotics : incidence, prevention and management. Drug Saf. 2005;28(3):191-208. [Medline].
Sachdev P, Mason C, Hadzi-Pavlovic D. Case-control study of neuroleptic malignant syndrome. Am J Psychiatry. Aug 1997;154(8):1156-8. [Medline].
Sakkas P, Davis JM, Janicak PG, Wang ZY. Drug treatment of the neuroleptic malignant syndrome. Psychopharmacol Bull. 1991;27(3):381-4. [Medline].
Sato Y, Asoh T, Metoki N, Satoh K. Efficacy of methylprednisolone pulse therapy on neuroleptic malignant syndrome in Parkinson's disease. J Neurol Neurosurg Psychiatry. May 2003;74(5):574-6. [Medline].
Schneider SM. Neuroleptic malignant syndrome: controversies in treatment. Am J Emerg Med. Jul 1991;9(4):360-2. [Medline].
Titier K, Canal M, Deridet E, et al. Determination of myocardium to plasma concentration ratios of five antipsychotic drugs: comparison with their ability to induce arrhythmia and sudden death in clinical practice. Toxicol Appl Pharmacol. Aug 15 2004;199(1):52-60. [Medline].
Trenton A, Currier G, Zwemer F. Fatalities associated with therapeutic use and overdose of atypical antipsychotics. CNS Drugs. 2003;17(5):307-24. [Medline].
Viejo LF, Morales V, Punal P, et al. Risk factors in neuroleptic malignant syndrome. A case-control study. Acta Psychiatr Scand. Jan 2003;107(1):45-9. [Medline].
Wilt JL, Minnema AM, Johnson RF, Rosenblum AM. Torsade de pointes associated with the use of intravenous haloperidol. Ann Intern Med. Sep 1 1993;119(5):391-4. [Medline].
Zetin M. Psychopharmacohazardology: major hazards of the new generation of psychotherapeutic drugs. Int J Clin Pract. Jan 2004;58(1):58-68. [Medline].
Further Reading
Keywords
neuroleptic agent toxicity, neuroleptic poisoning, major tranquilizers, antipsychotic drugs, phenothiazines, aliphatics, piperidines, piperazines, thioxanthenes, butyrophenones, dibenzoxazepines, dihydroindolone, diphenylbutylpiperidine, benzisoxazole, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, NMS, seizures, hypothermia, arrhythmias, respiratory depression, involuntary movement disorders, dystonia, torticollis, oculogyric crisis, opisthotonus, dysrhythmia, acute dystonia, parkinsonism, akathisia, tardive dyskinesia, dantrolene, tardive dyskinesia
