Adverse reactions and the possible mechanisms of the reactions caused by antipsychotics are reviewed. The mechanisms of many of these adverse reactions have not been elucidated to date, hence there have been inconsistent approaches to the problem. Complicated symptoms of the reactions, especially exacerbation of the mental state, are often considered to be a part of the psychosis under treatment. Some of the reactions are temporary, or the patient may develop tolerance to them so that an additional drug may not be necessary.
It is suggested that use of the minimum dosage of antipsychotics, avoidance of polypharmacy, and close observation of the patient constitute the best approach to the prevention of unwanted reactions.
Get full access to this article
View all access options for this article.
References
1.
AydF. J.Jr.: Neuroleptic-induced Extrapyramidal Reactions: Incidence, Manifestations and Management, Int. Drug Ther. Newsl.8: 77–88, 1973.
2.
CraneG.: Clinical Psychopharmacology In Its 20th Year, Science181: 124–128, 1973.
3.
EngelJ.LiljequistS.JohannsenK.: Behavioral Effects of Long Term Treatment with Antipsychotic Drugs, InVailG. SedUvnaesB.ZottermanY. (Eds): Antipsychotic Drugs Pharmacodynamics and Pharmacokinetics, Pergamon Press, Oxford, pp. 63–71, 1976.
4.
HarmatzJ. S.: Behavioral Toxicity, InShaderR. I.DimascioA. (Eds) Psychotropic Drug Side Effects, Clinical and Theoretical Perspectives, Baltimore, Williams and Wilkins, pp. 142–148, 1970.
5.
SinghM. M.: Dysphoric Response to Neuroleptic Treatment in Schizophrenia and Its Prognostic Significance, Dis. Nerv. Syst.37: 191–196, 1976.
6.
Neurological Syndromes Associated with Antipsychotic Drug Use (Editorial). Arch. Gen. Psychiatry28: 463–466, 1973.
7.
DavisJ. M.: Clinical Pharmacology and the Prescription of Psychotropic Medication, Pharmakosychiat. Neuro-Psychopharmakol.8: 332–339, 1975.
8.
WeissmanS. H.: The Incidence of Primary Psychiatric Illness in Women Attending a General Medical Clinic, Dis. Nerv. Syst.38: 150–153, 1977.
9.
AppletonW. S.: Third Psychoactive Drug Usage Guide, Dis. Nerv. Syst.37: 39–51, 1976.
10.
BerlingR.MjorndalT.OrelandL.: Plasma Levels and Clinical Effects of Thioridazine and Thioxanthine, J. Clin. Pharmacol.2: 178–186, 1975.
11.
SakuraiY.NakaharaT.TakahashiR.: Prediction of Response to Chlorpromazine in Schizophrenics, Psychopharmacologia44: 195–203, 1975.
12.
WallaceE. R.IVStantonM. A.: Acute Hypertension After Abrupt Withdrawal of Antipsychotic Medication, South. Med. J.70: 359–362, 1977.
13.
CurryS. H.MarshallJ. H. L.DavisJ. M.: Chlorpromazine Plasma Levels and Effects, Arch. Gen. Psychiatry22: 289–296, 1970.
14.
ManP. L.ChanC. H.: Severe Shock Caused by Chlorpromazine Hypersensitivity, Br. J. Psychiatry122: 185–187, 1973.
15.
CancroR.WilderR.: A Mechanism of Sudden Death in Chlorpromazine Therapy, Am. J. Psychiatry127: 368–371, 1970.
16.
AydF. J.Jr.: Cardiovascular Effects of Phenothiazines, Int. Drug Ther. Newsl.5: 1–8, 1970.
17.
StephensonJ. B. P.: Anoxic Seizure or Epilepsy?Br. Med. J.2: 45, 1977.
18.
ThomasJ. E.: Episodic Unconsciousness: A Sign of Epilepsy or Syncope?Medical Opinion2: 1–4, 1974.
19.
RifkinA.QuitkinR.CarrilloC.: Very High Dosage Fluphenazine for Non-Chronic Treatment Refractory Patient, Arch. Gen. Psychiatry26: 398–402, 1971.
SakalisGCurryS. H.MouldG. P.: Physiologic and Clinical Effects of Chlorpromazine and Their Relationship to Plasma Level, Clin. Pharmacol. Ther.13: 931–941, 1972.
29.
AydF. J.Jr.: Haloperidol: Fifteen Years of Clinical Experience, Dis. Nerv. Syst.33: 459–469, 1972.
30.
WestlakeR. J.RastegarA.: Hyperpyrexia From Drug Combination, J. Am. Med. Assoc.225: 1250, 1973.
31.
ElliotC. F.BroeG. A.: Hyperpyrexia and Phenothiazine Medication, Med. J. Aust.1: 462, 1973.
32.
ShapiroM. F.: Despair, Trifluoperazine, Exercise and Temperature of 108°F, Am. J. Psychiatry124: 705–709, 1967.
MartinJ. B.: Neural Regulation of Growth Hormone Secretion. N. Engl. J. Med.228: 1384–1393, 1973.
35.
VinarovaM.TachezyR.: Galactorrhea in Patients Treated with Psychotropic Drugs, Arch. Nerv. Sup. (Praha)7: 248–250. 1965.
36.
ByckR.: Drugs and the Treatment of Psychiatric DisordersInGoodmanL. S.GilmanA. (Eds): The Pharmacological Basis of Therapeutics, 5th ed., MacMillan Publishing Co.New York, N.Y. 10022, pp. 152–200, 1975.
37.
DavisJ. M.: New Antipsychotic Drugs, Curr. Psychiatr. Ther.17: 209–218, 1977.
38.
Haloperidol in Psychiatry, The Medical Letter17: 11–12. 1975.
Molindone—A New Antipsychotic Drug. The Medical Letter17: 56–60, 1975.
41.
LitbackR.KaelblingR.: Agranulocytosis, Leukopenia and Psychotropic Drugs, Arch. Gen. Psychiatry24: 265–267, 1971.
42.
EbertM.ShaderR. I.: Hematological Effects, InShaderR. I.DimascioA. (Eds): Psychotropic Side Effects, Williams & Wilkins, Baltimore, pp. 164–174, 1970.
43.
PisciottaA. V.: Drug Induced Leukopenia and Aplastic Anemia, Clin. Pharmacol. Ther.12: 13–43, 1971.
44.
DucombL.BaldessariniR. J.: Timing and Risk of Bone Marrow Depression by Psychotropic Drugs, Am. J. Psychiatry134: 1294–1297, 1977.
45.
SweetC.Jr.: Outpatient Phenothiazine Use and Bone Marrow Depression, Arch. Gen. Psychiatry30: 1416–1418, 1975.
46.
GunbyB.SandvigK.Steenfeldt-FossO. W.: Late Oculocutaneous Complication in Phenothiazine Therapy, Acta Psychiatr. Scand.42: 97–102, 1966.
47.
LjunggrenB.MoellerH.: Phenothiazine Phototoxicity: An Experimental Study on Chlorpromazine and Related Tricyclic Drugs, Acta Dermatovener (Stockholm)57: 325–329, 1977.
48.
PolvanN.AkpinarS.AhmedM. B.: Different Effects of Trifluoperazine When Administered Daytime or Night, Br. J. Psychiatry119: 601–602, 1971.
49.
FlemenbaumA.: “Pavor Nocturnus” A Complication of Single Daily Tricyclics or Neuroleptic Dosage, Am. J. Psychiatry133: 570–572, 1976.
50.
SimpsonG. M.CooperT. A.: Clozapine Plasma Levels and Convulsions, Am. J. Psychiatry135: 99–100, 1978.
51.
MartinE. M.MartinR. D.: Hazards of Medication, J. B. Lippincott, Philadelphia, 1971.
52.
DominoE. F.: Antipsychotics: Phenothiazines, Thioxanthenes, Butyrophenones, and Rauwolfia AlkaloidsInDipalmaJ. R. (Ed): Drill's Pharmacology in Medicine, 4th Ed., McGraw-Hill Book Co., New York, pp. 463–488, 1971.
GordosG.OrzackM. H.ColeJ. O.: The Importance of Dose in Antipsychotic Drug Administration — A Review of Dose-response Studies, Psychopharmacologia29: 221–230, 1973.
55.
DavisJ. M.: Recent Developments in The Treatment of Schizophrenia. Psychiatric Annals6: 71–111, 1976.
56.
DalbyM. A.: Behavioral Effects of Carbamazepine, Adv. Neurol.11: 331–344, 1975.
57.
GardosG.ColeJ. O.: Maintenance Antipsychotic Therapy: Is the Cure Worse Than the Disease?Am. J. Psychiatry133: 32–36, 1976.
58.
KitamuraT.: Is the “Drug Holiday” Harmful?Keio J. Med.25: 131–137, 1976.
59.
HaasH. J.JansenP. A. J.: The Action of Neuroleptic Drugs, North Holland Publishing, Amsterdam, 1965.
60.
ChaffinD. S.: Phenothiazine-induced Acute Psychotic Reaction: The Psychotoxicity of a Drug, Am. J. Psychiatry121: 26–32, 1964.
61.
ItilT. M.SaletuB.HsuW.: Clinical and Quantitative EEG Changes at Different Dosage Levels of Fluphenazine Treatment, Acta Psychiatr. Scand.47: 440–451, 1971.
62.
StilleG.: Neurophysiological Correlates to Antipsychotic Effects of Drugs, InVeilG. SedUvnaesD.ZottermanY. (Eds): Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics, Pergamon Press, Oxford, pp. 51–61, 1976.
63.
BunneyB. S.AghajanianA.: The Effects of Antipsychotic Drugs on the Firing of Dopaminergic Neurons: A Reappraisal, InVeilG. SedUvnaesD.ZottermanY. (Eds): Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics, Pergamon Press, Oxford, pp. 305–318, 1976.
64.
SimpsonG. M.AmusoP.BlairJ. H.: Aspects of Phenothiazine Produced Extrapyramidal Symptoms, Arch. Gen. Psychiatry10: 199–208, 1964.
65.
SimpsonG. M.Kunz-BartholineE.: The Relationship of Individual Tolerance Behavior and Phenothiazine Produced Extrapyramidal System Disturbance, Dis. Nerv. Syst.29: 269–274, 1968.
66.
AlpertM.DiamondF.KesselmanM.: Correlation Between Extrapyramidal and Therapeutic Effects of Neuroleptics, Comp. Psychiatr.18: 333–336, 1977.
67.
HippiusH.: On the Relation Between Antipsychotic and Extrapyramidal Effects of Psychoactive Drugs, InVeilG. SedUvnaesB.ZottermanY. (Eds): Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics, Pergamon Press, Oxford, pp. 437–445, 1976.
68.
HollisterL. E.: Clinical Use of Psychotherapeutic Drugs, Charles C Thomas, Springfield, Ill. pp. 13–55, 1976.
KlettC. J.CaffeyE.: Evaluating the Long Term Need for Antiparkinson Drugs by Chronic Schizophrenics, Arch. Gen. Psychiatry26: 374–379, 1972.
71.
ChienC-PDimascioA.: Drug Induced Extrapyramidal Symptoms and Their Relation to Clinical Efficacy, Am. J. Psychiatry123: 1490–1498, 1966.
72.
ConeyA. H.DavidsonC.GastelR.: Adaptive Increase in Drug Metabolizing Enzymes Induced by Phenobarbital and Other Drugs, J. Pharmacol. Exp. Ther.130: 1–8, 1960.
73.
Rivera-CalminL.CastanedaL.LasagnaL.: Effects of Mode of Management on Plasma Chlorpromazine in Psychiatric Patients, Clin. Pharmacol. Ther.14: 978–986, 1973.
74.
Yaryura-TobiasJ. A.FledelNezirogluT.: Vitamins, Neuroleptics and Antiparkinson Drugs in Catecholamine Excretion, Biochem. Psychiatry11: 363–366, 1976.
75.
SinghM. M.KayS. R.: Therapeutic Reversal with Benztropine in Schizophrenics, Practical and Theoretical Significance, J. Nerv. Ment. Dis.160: 258–266, 1975.
76.
AydF. J.Jr.: Do Antiparkinson Drugs Interfere with the Therapeutic Effects of Neuroleptics?Int. Drug Ther. Newsl.9: 29–32, 1974.
77.
VilleneuveA.: The Rabbit Syndrome a Peculiar Extrapyramidal Reaction, Can. Psychiatr. Assoc. J.Suppl. 2: 69–72, 1972.
78.
JusK.JusA.GautierJ.: Studies on the Action of Certain Pharmacological Agents on Tardive Dyskinesia, Int. J. Clin. Pharmacol. Ther. Toxicol.9: 138–145, 1974.
79.
SovnerR.DimascioA.: The Effect of Benztropine Mesylate in the Rabbit Syndrome and Tardive Dyskinesia, Am. J. Psychiatry134: 1301–1302, 1977.
80.
CraneG. E.: Persistent Dyskinesia, Br. J. Psychiatry122: 395–405, 1973.
81.
AsnisG. M.LeopoldM. A.DuvoisinR. C.: A Survey of Tardive Dyskinesia in Psychiatric Outpatients, Am. J. Psychiatry134: 1367–1370, 1977.
82.
FannW. E.LakeC. R.: On the Co-existence of Parkinsonism and Tardive Dyskinesia, Dis. Nerv. Syst.35: 324–326, 1974.
83.
QuitkinF.RifkinA.GochfieldL.: Tardive Dyskinesia: Are First Signs Reversible?Am. J. Psychiatry134: 84–87, 1977.
KobayashiR. M.: Drug Therapy of Tardive Dyskinesia, N. Engl. J. Med.296: 257–260, 1977.
86.
JestaD. V.: Masking of Tardive Dyskinesia with Four Times a Day Administration of Chlorpromazine. Dis. Nerv. Syst.38: 755–758, 1977.
87.
LaduronP. M.LeysenJ. E.: Is the Low Incidence of Extrapyramidal Side Effects of Antipsychotics Associated with Antimuscarinic Properties?J. Pharm. Pharmacol.30: 120–122, 1978.
88.
IversenL. L.HornA. S.MillerR.: Structure-activity Relationships for Interactions of Agonist and Antagonist Drugs with Dopamine-stimulated Adenyl Cyclase of Rat Brain — A Model for CNS Dopamine Receptors?InVeilG. SedUvnaesB.ZottermanY. (Eds): Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics, Pergamon Press, Oxford, pp. 285–303. 1976.
89.
SayersA. C.BuerkiH. R.: Antiacetylcholine Activities of Psychoactive Drugs: A Comparison of the (H3) Quinuclidinyl Benzilate Binding Assay with Conventional Methods, J. Pharm. Pharmacol.28: 252–253, 1976.
90.
PrienR. F.CaffeyE. M.: Guidelines for Antipsychotic Drug Use, Research Report #95, Veterans Administration, Perry Point, Md., 1974.
91.
GardosG.: Are Antipsychotic Drugs Interchangeable?J. Nerv. Ment. Dis.159: 343–348, 1974.
92.
LehmanH. E.: Psychopharmacological Treatment of Schizophrenia, Schizophrenia Bull.13: 27–45, 1975.
ChaseT.: Antipsychotic Drugs. Dopaminergic Mechanism and Extrapyramidal Function in Men, InVeilG. SedUvnaesD.ZottermanY. (Eds): Antipsychotic Drugs, Pharmacodynamics and Pharmacokinetics, Pergamon Press, Oxford, pp. 321–329, 1976.
95.
SnyderS. H.: Neuroleptic Drugs and Neurotransmitter Receptors, J. Cont. Educ. Psychiatry39: 21–31, 1978.
