Method Clozapine OD case reports [Conclusion: not reliable]

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Clozapine OD case reports

Hello, some people were asking about clozapine OD.

Here are some medical case reports.

From 2003 to 2009 clozapine was the reason of 99,7% criminal poisonings in Moscow, Russia.

Death caused by criminal poisonings were in 0,1% cases, not criminal – from 10% to 18%.

WARNING!

THIS TEXT CONTAINS MEDICAL TERMINOLOGY AND MAY BE HARD TO DIGEST. DO NOT READ IT IF YOU ARE NOT FEELING UP TO.

ALSO WANTED TO REMIND YOU THAT USING THE UNKNOWN METHODS IS ALWAYS A GAMBLE.

DO NOT TRY TO SWALLOW ANY RANDOM STUFF HOPING THAT YOU WILL DIE!​

MY CONCLUSION IS: METHOD DOES NOT GUARANTEE DEATH, FAR FROM PEACEFUL, IN SOME CASES IT WAS EXTREMELY LARGE TIME-SPAN DESPITE SUCCESSFUL CTB ATTEMPTS BELOW. INSTEAD OF GAMBLING, IT WOULD BE MUCH BETTER TO USE BETTER KNOWN METHODS…

A 14-year-old girl developed various toxicities after ingesting a potentially lethal dose of clozapine.​

The girl ingested clozapine 3000mg (approximately 62.5 mg/kg) in the evening. THE NEXT MORNING, she developed increasing loss of consciousness and agitation. She was admitted with coma, respiratory depression and recurrent seizures 18 to 20 hours after clozapine ingestion. Her clozapine plasma level was still highly toxic on day 3, correlating with tachycardia and persistent cerebral depression. She later developed pancreatitis, high fever, aspiration pneumonia and rhabdomyolysis with transient renal failure. The girl received supportive therapeutic measures. Her clozapine plasma level reached the upper therapeutic limit on day 5. On day 9, she was transferred for psychiatric treatment.

Note: 3000 mg of clozapine is a potentially lethal dose. However, as we can see, the girl took the dose in the evening and after 18-20 hours she was still alive, so I would give zero for both speed and reliability. We don't have so much time, a great possibility to be found.

A 25-year-old man died 5 hours after ingesting clozapine ('Clozaril') 2g.​

The man was brought to the emergency room approximately 3 hours after ingesting the overdose. He was agitated, confused, combative and uncooperative. Four hours after overdose the patient's blood clozapine concentration was 1.94 mcg/ml. Gastric lavage was performed and large amounts of pill fragments were recovered. The patient became unresponsive without a pulse 1 hour later. CPR was initiated but the patient DIED. A postmortem blood clozapine concentration was 5.81 mcg/ml.

Note: 3 hours passed, he was still conscious, agitated and combative. It is far from a peaceful death, but he somehow managed to die 5 hours after ingestion. Even despite gastric lavage. I think we should not treat this as a story of success because it is more about the patient's luck.

Clozapine overdose. Seizures, coma and tachycardia: case report​

A 23-year-old woman, who was schizophrenic, survived an overdose of clozapine [dose not stated] despite high concentrations of clozapine in her serum and urine. The patient had been successfully treated with clozapine 75–300 mg/day for approximately 5 years. However, her medical condition worsened and she attempted suicide by taking an overdose of clozapine. She had seizures and was in a coma on admission to hospital. Her serum level of creatine phosphokinase increased to 15 200 IU/L on hospital day 7, and decreased to 485 IU/L 7 days later. The woman had sinus tachycardia, but no evidence of agranulocytosis. She regained consciousness on the fourth hospital day and was discharged to a psychiatric clinic 11 days later. The woman's serum clozapine concentrations 3 and 32 hours after the suicide attempt were 3.62 and 1.10 µg/ml, respectively. Her urinary clozapine concentration 32 hours after the clozapine overdose was 4.28 µg/ml.

Note: this case does not give us a lot of necessary information. Everything we know is that she survived the attempt and reached coma state.

A 34-year-old woman with schizoaffective disorder survived an overdose of clozapine 6–8g.​

The patient was hospitalised in a deep coma 1 hour after she intentionally ingested the clozapine tablets. Her BP, HR, ECG and chest x-ray were all normal. She underwent gastric lavage and standard resuscitation. Her plasma concentrations of clozapine at 14, 18 and 26 hours after ingestion were 5.7, 3.7 and 2.8 mg/ml, respectively. On the sixth hospital day, the patient developed sudden hypotension with abundant haematemesis, which persisted for 2 days despite treatment with somatostatin. An erosive haemorrhagic gastritis was evident on gastroscopic examination. The woman was discharged from hospital after 13 days. Author comment: 'There are reports of clozapine-induced delirium reversed with physostigmine; the present case, however, did not show severe central or peripheral anticholinergic symptoms. It appears, in accordance with the literature, that early treatment of overdose complications is successful under a standard approach, making the case for clozapine as a relatively safe drug.'

Note: she was hospitalized in a deep coma 1 hour after… A case when somebody saved a person. Though 6-8 g of clozapine is much more than a lethal dose. One more case about how important to have a decent time-span before being found.

Clozapine overdose case report​

A 47-year-old woman was found dead following clozapine overdose [details of drug administration not stated]; her death was attributed to the combined effect of clozapine toxicity and haemorrhage due to self-inflicted blunt cranial trauma. Her medical history included schizophrenia and a previous suicide attempt by overdose. Fifty empty blister packs of clozapine were found in the vicinity of her body, and post-mortem toxicological analyses detected a lethal concentration of clozapine in her blood. Author comment: "Death was attributed to the combined effects of clozapine toxicity and haemorrhage due to blunt cranial trauma."

Note: as far as we don't know what was the influence of self-inflicted blunt cranial trauma, we cannot state that clozapine would be successful alone. Probably It was a lethal combination.

Clozapine overdose in a suicide attempt: case report​

A woman [age not stated] developed fatal drug intoxication following excessive ingestion of clozapine in a suicide attempt. On 28 May 2011, an anonymous complaint of a foul odour, emanating from a rental unit, led to a police investigation. The body of a woman was found on the floor in the toilet in prone position, and the body was in an advanced state of decomposition with pooled body fluid beneath it. An autopsy found no signs of mechanical injuries. Toxicology analysis found high levels of clozapine. The drug was detected in the gastric contents, liver tissues, blood and pleural effusion, and the clozapine content in the left pleural effusion was 29.6 µg/mL, exceeding 49 times of the toxic dose (0.6 µg/mL). Moreover, alcohol [ethanol] was also detected in the pleural effusion. Based on the autopsy results and other findings such as the surveillance video and a lack of food in the rental room, the investigators confirmed suicidal death on the night of 21 May 2011 (estimate postmortem interval: 7 days) caused by excessive consumption of clozapine and alcohol. Author comment: "[A] female body discovered in her room after she committed suicide by consuming excessive clozapine." "The toxicology analysis found high levels of clozapine". "[C]lozapine content in the left pleural effusion was 29.6 µg/ml, exceeding 49 times of the toxic dose (0.6 µg/ ml)."

Note: this case is showing how it is important to have a large amount of time avoiding being found before death. A person was found only a week after.

Clozapine overdose. Seizure and junctional tachycardia: case report​

A 25-year-old man developed seizure and junctional tachycardia following a voluntary overdose of clozapine. The man presented with seizure after presumed ingestion of 5 gm of clozapine. He was being treated for schizophrenia, complicated by multiple suicide attempts. His medications included clozapine 400 mg/day [initial route not stated], sodium valproate, zopiclone and biperiden. Initial examination revealed Glasgow score of 12, a pulse of 160 beats/min, and blood pressure of 60/40 mmHg, that resolved after administration of crystalloid solution and colloid solution. An ECG revealed tachycardia with narrow QRS and a normal axis with absent P-wave, suggesting junctional nodal reentrant or atrial tachycardia. A clozapine plasma concentration taken after 4.5 hours revealed supra therapeutic value of 6357 microg/L. The man was given gastric lavage on admission and was treated with diltiazem and atenolol. His tachycardia finally dropped and completely resolved after 40 hours of hospitalization and the heart returned to normal sinus rhythm without any related electrical anomalies. Author comment: "We report a case of junctional tachycardia (JT) induced by clozapine overdose in the context of a voluntary drug overdose."

Note: 5 gm of clozapine is more than a fatal dose, however this person recovered after OD. As long as we don't know the time from ingestion to presentation to hospital, we cannot reach any more conclusions.

Maternal death, fetal distress and delayed neonatal peristalsis: case report​

A 16-year-old pregnant girl died of multiple organ failure after taking an overdose of clozapine in an attempted suicide. A live baby girl was delivered by caesarean section due to signs of fetal distress determined by an abnormal cardiotocogram prior to birth and developed delayed peristalsis shortly afterwards, but survived without complications. The girl, who was admitted unconscious after taking approximately 10g of clozapine not prescribed to her, had a HR of 110 beats per minute, a BP of 90/60 mmHg, oxygen saturation 75% on room air and 90% on high flow oxygen, a respiratory rate of 20 breaths per minute, blood sugar of 7.0 mmol/L, and a Glasgow coma score of 8. Examination revealed bilateral crepitations in her lungs. She was ventilated and given supportive treatment. Her full blood count, renal and liver function tests, and plasma cholinesterase activity tests were normal. Toxicological tests were negative for paracetamol [acetaminophen], salicylate, tricyclic antidepressant, ethanol, phenytoin, carbamazepine and valproic acid. Ultrasound examination of her distended abdomen showed a 32-week-old fetus weighing approximately 1.7 kg, with a fetal HR of 145 beats per minute and a normal amniotic fluid index. The adolescent girl developed hypotension 28 hours later. The cardiotocogram of the fetal heart indicated low fetal HR variability and absence of accelerations for 90 minutes, therefore a caesaran section was performed, delivering a live baby girl with an Apgar score of 7 at 5 minutes. The baby developed abdominal distention on the first day of life and treatment with IV fluids and antibiotics was initiated due to suspected necrotising enterocolitis. The baby did not pass stool for a further 48 hours and no bowel sounds were detected. At this point, it became apparent that the baby had developed anticholingeric side-effects of clozapine in the form of delayed peristalsis. The baby's symptoms resolved within a week of beginning treatment and bowel function returned to normal. The mother developed adult respiratory distress syndrome, hypotension, and renal failure. Despite continued support, she died 42 days after admission. Clozapine and its metabolites were detected in urine of the mother on day 3 and in the baby's urine on day 6 after maternal intake. Author comment: "Clozapine crosses the placental barrier and can cause toxic effects in the fetus/newborn baby. It should be remembered as a rare cause of delayed peristalsis in a newborn baby."

Note: despite helping mother, she died… 42 days after admission. I think 42 days is too much. 10 g of clozapine is much more than a lethal dose. I suppose if she was not found in time, she would have all chances to die.

Clozapine overdose. Delirium, rhabdomyolysis and tachycardia: case report​

A 36-year-old man developed rhabdomyolysis, delirium and tachycardia following clozapine overdose. The man presented to the emergency department of the hospital due to altered consciousness and disorientation. He had intoxicated himself 2-4 hours prior with his current maintenance schizophrenic medication of oral clozapine 125mg tablets. His initial Glasgow Coma Score was 14. He was agitated and delirious. He showed tachycardia with a pulse of 145 /min, His serum creatinine kinase (CK) level was significantly elevated (9899 U/L). The man received initial treatment with normal saline and sodium bicarbonate for rhabdomyolysis and lorazepam for agitation. Approximately 10 hours after arrival at the emergency department, the analysis revealed extremely high plasma clozapine concentrations of 3177 µg/L (reference value: 200–600 µg/L). He was subsequently transferred to the intensive care unit for further treatment. After 2 days, his CK level decreased to 3450 U/L and 5 days after hospitalization, his clozapine plasma concentration decreased to non-toxic concentrations (153 µg/L). After the psychiatric evaluation, he was discharged with no somatic sequelae [not all outcomes stated]. Author comment: "According to the Naranjo probability scale, there was a probable relationship, i.e., score 6, between the development of rhabdomyolysis and clozapine overdose in this patient." "Clozapine is an antipsychotic drug with potentially harmful adverse effects. The most frequently reported symptoms in clozapine intoxication are impaired alertness and tachycardia."

Note: after 2-4 hours he was still conscious but having agitation, disorientation and delirium. 2 hours before reaching unconscious state is too much.

Clozapine overdose: case report​

A 37-year-old man developed CNS depression involving delirium and variety of anti-muscarinic events following clozapine overdose involving clozapine adulterated street drugs use. The man presented in an unconscious state with a bag of pink powder besides him. The emergency medical services found him to be obtunded with respiratory failure. He was administered with naloxone; however, he did not show any improvement. At the time of presentation, he was in comatose state and required emergent intubation due to respiratory failure and airway stabilization. Initially, he showed copious secretions which required oropharyngeal suctioning. He also showed miosis along with hypoactive bowels and relaxed neuromuscular tone. His electrocardiogram showed sinus tachycardia and QTc of 490ms. His urine drug screen was positive for benzodiazepines and comprehensive screen confirmed presence of methadone and clozapine which were not prescribed to him. Within 12 hours he became awake and was extubated; however, he required restraints due to paroxysms of agitated delirium interspersed with somnolence. His symptoms of miosis, tachycardia, absent bowel sounds and dry skin persisted and he developed fever. At this point, he also showed a very dry mouth. The man was administered with physostigmine which resulted in dramatic lucidity with marked improvement in level of consciousness, heart rate and normal salivation. His restraints were removed. He eventually admitted to buying a powder which was told to contain heroin and benzodiazepines (it did not contain heroin) but suspected to have contained only clozapine [route, amount used and time to reactions onsets not stated]. He did not require further antidote and was subsequently discharged [not all outcomes stated].

Note: respiratory failure is a good sign because after that there is not much time left until death. Though, it was an accidental overdose. But what was the dose if he had respiratory arrest? This is a bit strange.

Clozapine. Hyperactive delirium, worsening of cosnsciousness and stupor: case report​

A 50-year-old man developed hyperactive delirium, worsening of consciousness and stupor due to clozapine intoxication following an overdose of clozapine. The man had mental retardation and schizophrenia, and he had been receiving treatment with clozapine 300 mg/day. Subsequently, he was hospitalised after an intoxication with 4200mg clozapine. He developed complications of intoxication 15 hours after the intoxication. At the current admission, his consciousness shifted from stupor to confusion. Additionally, he had disorientation, dysarthria, visual hallucinations and psychomotor agitation, and he needed physical restraint. Investigations of vital parameters revealed tachycardia. ECG revealed no significant alterations. Laboratory tests revealed mildly elevated creatine kinase only. He was diagnosed with hyperactive delirium secondary to severe clozapine intoxication. He remained haemodynamically stable over the first 9 hours. In view of the continued signs of hyperactive delirium, the man was shifted to the psychiatric unit. His clozapine blood level was noted to be elevated. About 15 hours postadmission, his consciousness worsened to severe stupor. He was then shifted to the ICU for life support and monitoring. His clozapine blood levels at 12 hours after the initial measurement was higher than the previous level. Subsequently, his level of consciousness improved, and he was shifted to the psychiatric unit again. His clozapine blood level after 27 hours were still higher that the level noted at admission. After 4 days of monitoring, the symptoms and the vital parameters improved, and a complete remission of psychomotor agitation was noted. His clozapine blood level at 105 hours post-admission was noted to be decreased. He was clearly conscious and co-operative, and the psychiatric examination revealed no alterations. Seven days postintoxication, clozapine was re-initiated at the usual dose of 300 mg/day.

Note: 15 hours after taking lethal dose and still alive. This is definitely an argument against reliability of the method.

A 15-year-old girl had ingested an unknown quantity of 100 mg Leponex tablets in a suicide attempt. ​

An empty prescription vial was found at the scene. Leponex is available in tablets of 25 and 100 mg for oral administration. The girl had unsuccessfully attempted suicide by consuming household cleaners and by jumping off a railroad viaduct. Her psychiatrist had then started her on treatment with Leponex. When hospitalized, the patient suffered from convulsions on all extremities and was unconscious. The convulsions ceased after administering diazepam. In the course of the reanimation the girl's circulation was unstable, she became bradycardic (50 beats/min) and again showed signs of convulsions which ceased after another diazepam injection. Because of deterioration in her spontaneous respiration the patient was endotracheally intubated and artificial respiration was applied. Cardiac massage had to be performed when the pulse rate slowed dramatically. Activated charcoal was given in an attempt to adsorb the neuroleptic drug. Gastric lavage could not be performed due to the danger of aspiration. Treatment with dopamine, adrenaline, noradrenaline and atropine did not lead to a stabilization of the circulatory conditions. During reanimation the girl developed a massive edema of the lung. All attempts to reanimate the patient did not lead to the anticipated clinical improvement and the girl died due to acute respiratory failure and cardiac arrest after 4 h of intensive care.

Note: this was a successful CTB case with respiratory failure and cardiac arrest. But taking into account the age of a girl, we cannot make a projection on ourselves.