|Year : 2016 | Volume
| Issue : 4 | Page : 1116-1121
Evaluation of acute antipsychotic poisoned cases
Samy A El-Hady Hammad, Naira F Girgis, Safaa A Zaher Amin, Azza W Zanaty, Haidy M. A. El-Kawy Abou Hatab MBBCh
Department of Forensic Medicine & Clinical Toxicology, Menoufia University Hospital, Menoufia, Egypt
|Date of Submission||30-Nov-2014|
|Date of Acceptance||02-May-2015|
|Date of Web Publication||21-Mar-2017|
Haidy M. A. El-Kawy Abou Hatab
Shebin Elkoom, Menoufia, 32511
Source of Support: None, Conflict of Interest: None
The aim of this work was to evaluate acute antipsychotic poisoned cases through studying all patients admitted at Menoufia Poison Control Center over 1 year regarding sociodemographic factors (age, sex, residence); mode of exposure; clinical manifestations (symptoms and signs); and the relation between antipsychotic drug overdose and severity grades of the studied cases, according to poison severity score.
Toxicological exposures and fatalities associated with neuroleptic agents continue to increase in the world in past 10 years. Consequently, it is important for the practising clinician to be familiar with the pharmacology and toxicology of these medications.
Materials and methods
The study was conducted on patients who arrived at Menoufia Poison Control Center with antipsychotic poisoning seeking for medical advice throughout 1 year (from 1 October 2012 to 30 September 2013). The data were collected from a previously designed clinical admission sheet (including the patient's age, sex, history, and clinical assessment data) and from investigations results.
The suicidal mode of poisoning comprised the highest frequency. Cases under 10 years old had taken the overdose accidentally, and all cases of 10 years old or more had taken the dose intentionally to commit suicide. Female cases had the highest percent of suicidal mode and male cases in accidental and homicidal mode. Palpitation and abnormal movements were the most common symptoms. According to poison severity score, most of the cases were of moderate degree, and the least were of severe and fatal degrees. Sinus tachycardia was the most prominent of the ECG changes.
Antipsychotic overdose produces a gamut of manifestations that affect multiple organ systems. The most serious toxicity involves the cardiovascular system and the central nervous system. Acute overdose seldom results in death.
Keywords: acute, antipsychotics, toxicity-overdose poisoning
|How to cite this article:|
El-Hady Hammad SA, Girgis NF, Zaher Amin SA, Zanaty AW, El-Kawy Abou Hatab HM. Evaluation of acute antipsychotic poisoned cases. Menoufia Med J 2016;29:1116-21
|How to cite this URL:|
El-Hady Hammad SA, Girgis NF, Zaher Amin SA, Zanaty AW, El-Kawy Abou Hatab HM. Evaluation of acute antipsychotic poisoned cases. Menoufia Med J [serial online] 2016 [cited 2020 Jun 1];29:1116-21. Available from: http://www.mmj.eg.net/text.asp?2016/29/4/1116/202527
| Introduction|| |
Tranquilizers induce tranquility in an individual. It is divided into: minor tranquilizer, which usually refers to anxiolytic or antianxiety agent used to cure dysentery in the 1940s; and major tranquilizer, which usually refers to antipsychotics or neuroleptics .
Neuroleptics are used as sedatives, tranquilizers, and as antiemetics to control hiccups, nausea, vomiting, and motion sickness. They are also used in the treatment of drug-induced psychosis and as adjuncts in the induction of anesthesia .
The first-generation neuroleptic agents ('typical' antipsychotics), also known as major tranquilizers, comprise a group of several classes of drugs (butyrophenones, dibenzoxazepines, dihydroindolone, diphenylbutylpiperidine, phenothiazines, thioxanthenes) .
Because of side effects of the first-generation neuroleptic agents, the newer second-generation antipsychotic agents ('atypical' antipsychotics) were introduced beginning in the 1970s. The newer agents include the following: benzepines, olanzapine, quetiapienethe etc. that lack extrapyramidal effects as rigidity, tremor, bradykinesia, akathesia etc, which commonly occur with the first-generation agents .
Trenton and Currier  reported that antipsychotic drug overdose could be diagnosed through clinical manifestations symptoms and signs that include anticholinergic effects, extrapyramidal symptoms, seizures, cardiac effects etc.
Toxicological exposures and fatalities associated with neuroleptic agents continue to increase in the world in past 10 years, for example: USA with 43 540 exposures, and six deaths in 2008. Consequently, it is important for the practising clinician to be familiar with the pharmacology and toxicology of these medications .
This study was conducted because of the increasing rate in antipsychotic poisoning cases arriving at Menoufia Poison and Dependence Control Center (MPCC).
| Materials and Methods|| |
This study had been conducted on patients arrived at MPCC complaining about antipsychotic drug overdose over 1 year (from 1 October 2012 to 30 September 2013). The data of the patients admitted were collected prospectively. The total number of patients was 60. Valid consent was taken from patients above the age of 21 years. For the patients below the age of 21, the consent was taken from their guardians to be involved in the study, after explaining to them the aim and methods of the work. The consent was designed by postgraduate and research unit in Faculty of Medicine, Menoufia University. Ethical approval was obtained from the ethics committee of Menoufia University. According to age, the patients were grouped into five groups:First: less than 5 years; Second: 5 to less than 10 years; Third: 10 to less than 20 years; Fourth: 20 to less than 40 years; and Fifth: 40 years or more. Clinical toxicological sheet was designed to be fulfilled for every patient and include all patient data from admission till discharge with regard to sociodemographic data of the patients: age, sex, residence etc. Data for patient assessment were represented as present history (including poison data with regard to its type, route, and mode of exposure). Data of clinical assessment comprised complete review of all body systems (general, neurologic, respiratory, and cardiovascular). Data regarding investigations included routine and specific ones. Data related to the outcome included ECG apparatus, arterial blood gas (ABG) analyzer, and TOXI-LAB instrument for the detection of antipsychotics. The studied cases were classified according to poison severity score (PSS). The clinical severity of poisoning was graded according to the method described by Persson et al.  and developed by the International Program on Chemical Safety, the European Community, and the European Association of Poisons Centers and Clinical Toxicologists (IPCS/EC/EAPCCT). The PSS is a four-scale grading as 0, none; 1, minor; 2, moderate; 3, severe; and 4, fatal. It was determined at the time of initial inquiry and following recovery, using examination findings including the Glasgow coma score, pupil size, convulsion, respiratory rate, pulse rate, blood pressure, body temperature, ECG findings and pH, and bicarbonate in ABGs. Arterial blood sample for ABG when needed. ECG was performed for each patient and was thoroughly analyzed. The data collected were tabulated and analyzed by statistical package for social science, version 17.0 on IBM-compatible computer (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp., USA).
| Results|| |
There was a highly significant relation (P< 0.001) between age and mode of poisoning (suicidal and accidental, homicidal) where all of the cases below the age of 10 had taken the overdose accidentally, representing 84.1%. The highest percentage for patients committing suicide were the cases within the age group of 20 to less than 40 years, representing 42.5%. Regarding sex, there was a significant relation (P< 0.05) between mode of exposure and sex where the female cases had the highest percentage in suicidal mode, representing 75%, whereas the male cases had the highest percentage in homicidal and accidental mode, representing 100 and 73.3%, respectively. A significant relation (P< 0.05) was found between mode of exposure and residence where the accidental mode was higher in rural areas (89.4%). On the contrary, suicide was prominent in urban areas (75%) ([Table 1]).
Regarding PSS, 41.7% of the cases were of moderate grade, followed by cases of 'none' grade 30%. Minor grade cases of severity score represented 25%, and the least were cases of severe and fatal grade, representing 1.7% for each one [Figure 1].
There was a highly significant relation (P< 0.001) between severity grades of the studied cases according to PSS and coingestion (100%) of fatal grades, whereas 60% were of the moderate grade, 53.3% were of the minor grade, and 44.4% of 'none' grade. There was a highly significant relation (P< 0.001) between severity grades of the studied cases, according to PSS and patients who were on psychic therapy and received antipsychotic medications as all severe and fatal grades cases were receiving antipsychotic drugs as treatment. Then none, minor, and moderate grade represent 33, 20, and 16%, respectively. There was a significant relation between severity grades of the studied cases according to PSS and seasonal variations (P< 0.05). Summer represented 100% in severe and 100% in fatal cases, 55.6% of none grade, 44% of moderate grade, and 40% of minor grade ([Table 2]).
|Table 2 Relation between severity grades of the studied cases according to poison severity score and poison history|
Click here to view
A significant relation (P< 0.05) between severity grades of the studied cases according to PSS and loss of consciousness where cases of loss of consciousness were of severe and fatal degree, representing 100% for each, followed by 28% of moderate cases. Relation between severity grades of the studied cases according to PSS and convulsions was significant (P< 0.05) as it represented 100% of severe and fatal degrees for each and 48% for moderate degree. The table also showed a highly significant relation (P< 0.001) between severity grades of the studied cases according to PSS and palpitation, as it was only present in moderate cases, representing 60%. The relation between severity grades of the studied cases according to PSS and abnormal movements was highly significant (P< 0.001): it represented 60% of moderate cases ([Table 3]).
|Table 3 Relation between clinical manifestations of the studied cases and severity grades according to poison severity score|
Click here to view
The frequency of ECG changes of studied cases as sinus tachycardia represented 20% of cases, followed by wide QRS complex, prolonged QT interval, and depressed ST segment that were 6.7% for each, as shown in [Figure 2].
The relation between severity grades and outcome of the patients. The fatal case died, whereas the severe case improved. There were no deaths in none, minor, moderate, or severe cases [Figure 3].
| Discussion|| |
The relation between mode of drug poisoning and different age groups was highly significant, where all cases below the age of 10 years had taken the overdose accidentally. It could be owing to the fact that this age had increased activities and skills, causing more exposure to their environment .
In addition, Gupta et al.  stated that children lack discrimination between harmful and nonharmful things. Infants and small children are closer to the ground than older children; in addition, children have a natural exploratory curiosity and put everything in their mouth.
The predominance of age group 20 to less than 40 years old in the present study coincided with Batra et al.  who stated that the most affected age group was 21–30 years, followed by group 31–40 years.
On the contrary, suicidal attempts were more common among teenagers (between 12 and 17 years). Some may attempt suicide by drug overdose. The most common reason for drug overdose was taking drugs after the problems they faced mostly related to unhappy boyfriend/girlfriend relationship'; 'Unhappy relationship with family'; 'unhappiness at school'. Thirty-one percent of the cases had suicidal ideas .
Predominance of male cases in accidental poisoning was because of the fact that males are more active and tend to have more exploratory character than females in childhood .
The results also showed that: predominance of female cases in suicidal poisoning can be explained by failure in education for young females, a lower rate of employment, and suppression of personal freedom by parents . Moreover, oppressive attitude of the husband toward the wife, marriage at a young age, and being a housewife (not working) also has impacts on suicide attempts of women .
With regard to the relation between residence and mode of poisoning, accidental poisoning was higher in rural areas (89.4%); this can be explained by the rural nature of Menoufia governorate and low socioeconomic standards associated with low levels of education and culture. This in agreement with Garg and Verma  who stated that poisoning cases were more common in rural areas.
Suicidal poisoning was found more in urban areas (75%). This result was in accordance with the results reported by Cahfer and Ismail , who studied cases of acute poisoning and had found that 57.7% of cases came from city center.
With regard to the PSS,  the study showed that 41.7% of the cases were of moderate grade, followed by cases of 'none' grade (30%). Minor grade cases represented (25%), and the least were cases of severe and fatal grades represented (1.7%) for each one.
Classification of most of the cases as 'none' or minor grades may be referred to the small amount ingested or ingestion of irritant substance with vomiting most of the ingested agent immediately.
In addition, Gussow  added that these drugs have a high therapeutic index and their fatality rates are rare.
There is a highly significant relation between severity grades of the studied cases according to PSS and coingestion as all of fatal grades (100%), whereas 60% of the cases were of moderate grade, 53.3% of the minor grade, and 44.4% of the 'none' grade. This coincided with Olson  who stated that toxicity of antipsychotic medications may be increased by coingestion of other agents, particularly drugs with similar metabolic pathways such as lithium, cyclic or other antidepressants, and benzodiazepines.
The results showed that there was a highly significant relation between severity grades of the studied cases according to PSS and patients who were on psychic therapy and received antipsychotic medications as 100% of the severe and fatal grades cases were receiving the drugs as treatment, whereas the none, minor, and moderate grades represent 33, 20, and 16%, respectively. One usual way of schizophrenic patients for attempting suicide is taking overdoses of drugs which they can easily access. Thus, among these patients, an acute intoxication with one of the psychotropic drugs on the market may be expected .
There was a significant relation between severity grades of the studied cases according to PSS and seasonal variations. Summer was the most common season for overdose, representing 100% of severe and fatal cases, 55.6% of none grade, 44% of moderate grade, and 40% of minor grade. These results were in accordance with that published by Oguche et al.  as they stated that highest frequency of admission was recorded during hot and dry months of March to June. Several explanations have been put forward. Children on summer holidays are more likely to be outdoors or to be left at home un attended or in the care of an older child or elderly relatives.
According to our observations for the cases admitted to MPCC, during summer owing to the results of examinations that appear for secondary schools and universities, suicidal attempts increase due to failure in examinations for fear of guilt or to escape punishment.
Concerning central nervous system manifestations in antipsychotic overdose cases, 59.2% had loss of consciousness, where most cases of loss of consciousness were of severe and fatal degree, representing 100% for each, followed by 28% of moderate grade cases. These manifestations could be explained by the centrally mediated sedation and diminished cerebral perfusion secondary to systemic hypotension and anticholinergic effects contributed to central nervous system depression caused by antipsychotics .
Impaired consciousness is a common and dose-dependent feature of antipsychotic overdose, ranging from somnolence to frank coma .
The table also shows a significant relation between severity grades of the studied cases according to PSS and convulsions as it represents 100% of severe and fatal degrees for each and 48% for moderate degree. Levine and Ruha  stated that the typical and atypical antipsychotics had the ability to lower seizure threshold and cause convulsions.
The table also shows a highly significant relation between severity grades of the studied cases according to PSS and palpitation, as it was only presented in 60% of the moderate grade cases. Palpitation may reflect the anticholinergic effect of the drug, and reflex tachycardia can be due to hypotension, patient's pain, and anxiety .
Concerning abnormal movements, a highly significant relation between severity grades of the studied cases according to PSS and abnormal movements represented 60% of moderate grade cases. Levine and Ruha  reported that extrapyramidal syndromes is a common presentation of acute antipsychotic drug overdose.
The results showed that the frequency of ECG changes of studied cases as sinus tachycardia represented 20% of cases, followed by wide QRS complex and prolonged QT and depressed ST segment that were 6.7% for each.
This result was in agreement with Minns and Clark  who reported that the most common cardiovascular effects that occur after atypical antipsychotic overdose are tachycardia, mild hypotension, and prolongation of the QT interval. A1-receptor antagonism and muscarinic receptor antagonism may also contribute to the tachycardia. Peripheral vasodilatation with reflex tachycardia is commonly encountered in the resultant orthostatic hypotension .
The only case with fatal score had died. The mortality rate associated with these cases is low; one in 5000 reported exposures end in death. Various other ingestants are often involved in these cases .
In addition, this is against the US FDA , that issued a warning to health care professionals that conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis.
| Conclusion|| |
Antipsychotic overdose produces a gamut of manifestations that affect multiple organ systems. The most serious toxicity involves the cardiovascular system and the central nervous system. Toxicity increases with coingestion of other drugs that have similar metabolic pathways. Acute overdose seldom results in death.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry 2004; 65
Knight ME, Roberts RJ. Phenothiazine and butyrophenone intoxication in children. Pediatr Clin North Am 1986; 33
Haddad PM, Dursun SM. Neurological complications of psychiatric drugs: clinical features and management. Hum Psychopharmacol 2008; 23
Dubois D. Toxicology and overdose of atypical antipsychotic medications in children: does newer necessarily mean safer? Curr Opin Pediatr 2005; 17
Trenton A, Currier G, Zwemer F. Fatalities associated with therapeutic use and overdose of atypical antipsychotics. CNS Drugs 2003; 17
Second generation (atypical) antipsychotic medication poisoning; 2014. Available at: http://www. UpToDate.com
.[Last accessed on 2016 Jan 10].
Persson HE, Sjoberg GK, Haines JA, Pronczuk de Garbino J. Poisoning severity score. Grading of acute poisoning. J Toxicol Clin Toxicol 1998; 36
Al Hazmi AM. Patterns of accidental poisoning in children in Jeddah, Saudi Arabia. Ann Saudi Med 1998; 18
Gupta SK, Peshin SS, Srivastava A, Kaleekal T. A study of childhood poisoning at National Poisons Information Centre, All India Institute of Medical Sciences, New Delhi. J Occup Health 2003; 45
Batra AK, Keoliya AN, Jadhav GU. Poisoning: an unnatural cause of morbidity and mortality in rural India. J Assoc Physicians India 2003; 51
Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila) 2009; 47
Malangu N. Acute poisoning at two hospitals in Kampala-Uganda. J Forensic Leg Med 2008; 15
Schmidtke A. Perspective: suicide in Europe. Suicide Life Threat Behav 1997; 27
Bilgin M, Cenkseven F, Satar S. An analysis of parent-female adolescent relationships in female adolescent suicides. Crisis 2007; 28
Garg V, Verma SK. Original research paper trends of poisoning in rural area of South-West, Punjab. J Indian Acad Forensic Med 2010; 32
Cahfer G, Ismail H. Cases of acute poisoning in southeast Anatolia of Turkey. Cilt 2004; 31
Gussow LA. Atypical antipsychotic overdose:it is all about the receptors. Am J Psychiatry 2012; 34
Olson KR. Emergency evaluation. In: Olson KR et al
.eds Olson's poisoning and drug overdose. 6th ed. San Francisco, CA: Anderson IB, Benowitz NL; 2012. 1–68.
Bez YA, Donmezdil SW, SirA D. Suicide attempt with paliperidone overdose: a case report. Bulletin Clin Psychopharmacol 2010; 20
Oguche S, Bukbuk DN, Watila IM. Pattern of hospital admissions of children with poisoning in the Sudano-Sahelian North eastern Nigeria. Niger J Clin Pract 2007; 10
Lackey D. Antipsychotic drugs including phenothiazines. 6th ed. San Francisco, CA: McGraw-Hill Global Education Holdings, LLC; 2007. 200–205.
Goldfrank LR, RS Hoffman, Lewis S, NM Ann Howland, NA Lewin, E Flomenbaum. Goldfrank's manual of toxicologic emergencies 2007:583–590.
Levine M, Ruha AM. Overdose of atypical antipsychotics: clinical presentation, mechanisms of toxicity and management. CNS Drugs 2012; 26
Minns AB, Clark RF. Toxicology and overdose of atypical antipsychotics. J Emerg Med 2012; 43
Tan HH, Hoppe J, Heard K. A systematic review of cardiovascular effects after atypical antipsychotic medication overdose. Am J Emerg Med 2009; 27
US FDA expands antipsychotic drug warning. Reuters UK. Information for Healthcare Professionals Antipsychotics; 2008
Z Zakariaei, S Taslimi, MA Tabatabaie far, M Arghand Dargahi. Bilateral dislocation of temporo mandibular joint induced by haloperidol following suicide attempt: a case report. Acta Medica Iran 2012; 50
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]