Fatal water intoxication during olanzapine treatment: A case report

doi:10.1016/j.legalmed.2013.12.003

Legal Medicine

Volume 16, Issue 2, March 2014, Pages 89-91

https://doi.org/10.1016/j.legalmed.2013.12.003 Get rights and content

Abstract

A man in his twenties was diagnosed with schizophrenia in his late teens. The night before his death, his family reported he drank a large amount of water, vomited, collapsed, and snored loudly while sleeping, but they did not view the event seriously as he did it routinely. The following morning, he was found dead. Autopsy revealed hyponatremia by water intoxication as the cause of death. Water intoxication has various causes. In this case, 610 ng/mL olanzapine was detected in serum samples. Although this concentration is not as high as the fatal concentrations reported in past studies, it might have caused some adverse effects. Furthermore, the observation that excessive drinking behavior started after the dose of olanzapine was increased suggests a possibility that olanzapine aggravated water intoxication.

Introduction

Olanzapine is one of the most common antipsychotic drugs used for first-line treatment of schizophrenia in Japan. It is widely used worldwide as it can also be used to treat bipolar depression. Olanzapine has various affinities for multiple receptors, including those for dopamine D2, serotonin 5-hydroxytryptamine (HT)2A, 5-HT2C, 5-HT6, adrenaline alpha-1, histamine H1, and muscarine M1–M5 [1]. Therefore, olanzapine is associated with various clinical and toxic manifestations [2], [3], [4], [5], [6]. In particular, dry mouth caused by metabolic disorder, a known adverse effect of olanzapine, occurs significantly more frequently in patients treated with olanzapine than in those treated with other drugs. In this study, we report a case of death from water intoxication while receiving olanzapine treatment. Although various factors are known to cause water intoxication, an adverse effect of olanzapine in the present case might have aggravated water intoxication.

Section snippets

Case report

A man in his twenties who was diagnosed with schizophrenia at in his late teens had over the few months preceding his death drunk such large amounts of water that his abdomen was expanded and he had been vomiting and collapsing. The night before his death, his family reported he drank a large amount of water, vomited, collapsed, and snored loudly while sleeping, but they did not view the event seriously as he did it routinely. The following morning, he was found dead. He had no history of

Cadaveric study

To compare against the findings of the present case, postmortem changes in electrolyte concentrations were examined in the serum and vitreous humor obtained from 18 cadavers (15 males, 3 females; aged 25 ̃ 86 years, mean age of 60.88 years at time of death) at 1–10 days postmortem (Table 1). Cadavers with causes of death that may have affected body fluid composition were excluded.

Results

As shown in Table 2, the mean (±standard deviation) sodium concentration for the 18 cadavers was 108.4 ± 9.58 mEq/L in the serum, 129.44 ± 8.84 mEq/L in the right vitreous humor, and 132.76 ± 10.28 mEq/L in left vitreous humor, concentrations that were higher than in the present case.

Discussion

Although there is currently no established diagnostic standard for water intoxication, a diagnosis is based on the observation of behavior such as polyposia, blood test results such as hyponatremia, and previous clinical history such as epileptic stroke and disturbance of consciousness [7]. In the present case, a large amount of water was consumed before death, autopsy revealed edema in the brain and lung, and the vitreous sodium concentration, which has been shown to be relatively resistant to

Conclusion

The cause of death in this case was judged to be hyponatremia by water intoxication based on the results of the autopsy, biochemical examination, and drug test. Moreover, it is likely that an adverse effect of olanzapine in the present case might have aggravated water intoxication.

References (21)

C. Rummel-Kluge et al.
Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis
Schizophr Res
(2010)
N. Radojevic et al.
Forensic aspects of water intoxication: four case reports and review of relevant literature
Forensic Sci Int
(2012)
W.V. Vieweg et al.
Psychogenic polydipsia and water intoxication—concepts that have failed
Biol Psychiatry
(1985)
G.F. O’Malley et al.
Olanzapine overdose mimicking opioid intoxication
Ann Emerg Med
(1999)
E. Saar et al.
The time-dependent post-mortem redistribution of antipsychotic drugs
Forensic Sci Int
(2012)
N. Nagai et al.
Olanzapine
Nihon Rinsho
(2013)
M. De Hert et al.
Guidelines for screening and monitoring of cardiometabolic risk in schizophrenia: systematic evaluation
Br J Psychiatry
(2011)
Z. Thornton-Jones et al.
The atypical antipsychotic olanzapine enhances ingestive behaviour in the rat: a preliminary study
J Psychopharmacol
(2002)
M. Ota et al.
Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats
Clin Exp Pharmacol Physiol
(2002)
A.W. Hartfield et al.
Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat
Psychopharmacology
(2003)

There are more references available in the full text version of this article.

Cited by (13)

Vitreous humor endogenous compounds analysis for post-mortem forensic investigation
2020, Forensic Science International
The chemical and biochemical analysis of bodily fluids after death is an important thanatochemical approach to assess the cause and time since death. Vitreous humor (VH) has been used as a biofluid for forensic purposes since the 1960s. Due to its established relevance in toxicology, a literature review highlighting the use of VH with an emphasis on endogenous compounds has not yet been undertaken. VH is a chemically complex aqueous solution of carbohydrates, proteins, electrolytes and other small molecules present in living organisms; this biofluid is useful tool for its isolated environment, preserved from bacterial contamination, decomposition, autolysis, and metabolic reactions. The post-mortem analysis of VH provides an important tool for the estimation of the post-mortem interval (PMI), which can be helpful in determining the cause of death. Consequently, the present review evaluates the recent chemical and biochemical advances with particular importance on the endogenous compounds present at the time of death and their modification over time, which are valuable for the PMI prediction and to identify the cause of death.
Relationship between polydipsia and antipsychotics: A systematic review of clinical studies and case reports
2020, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Citation Excerpt :
Fig. 1 shows the flow of the systematic literature search. Among 708 records, we identified and included 1 RCT (Goldman and Hussain, 2004), 4 single-arm trials (Canuso and Goldman, 1999; Kawai et al., 2002; Millson et al., 1996; Millson and Delva, 1999), 1 cross-sectional study (Serrano et al., 2014), 3 case series, not providing the detailed information of each case but reporting a summary of cases (Henderson and Goff, 1994; Peh et al., 1990; Spears et al., 1996), and 52 case reports (Adetoki et al., 2013; Afzal et al., 2007; Aguiar et al., 2015; Akkaya et al., 2006; Bersani et al., 2007; Caykoylu et al., 2009; Cecconi et al., 2016; Chiang et al., 2013; Costanzo et al., 2004; de Leon, 2003; Diniz et al., 2010; Dogangun et al., 2006; Ellinas et al., 1993; Faruqi and Mukkera, 2012; Fuller et al., 1996; Funayama et al., 2011; Girard-Martel and Gagnon, 2018; Gleadhill et al., 1982; Glusac et al., 1990; Godleski et al., 1989; Graham and Jawed, 1998; Gumber and Shah, 2014; Kar et al., 2002; Katsarou and Singh, 2010; Kern et al., 1997; Kruse et al., 2001; Landry, 1995; Li et al., 2012; Littrell et al., 1997; Looi et al., 1995; Margetic et al., 2006; Mauri et al., 2002; Mendelson and Deza, 1976; Nagasawa et al., 2014; Narendra et al., 2014; Nishikawa et al., 1991; Okazaki et al., 2007; Perestleo and Teixeira, 2016; Phull and Davies, 2011; Rao et al., 2011; Samaranayake et al., 2013; Secombe and Milne, 2016; Shen and Sata, 1983; Shenoi and Stockwell, 2015; Suzuki et al., 2008; Tanimoto et al., 1997; Tenyi and Voros, 2006; Wicki et al., 1998; Williamson et al., 2015; Zaidi, 2005; Zilles et al., 2010; Zink et al., 2004). Table 1 summarizes the findings of the identified 1 double-blind RCT, 4 single-arm trials, 1 cross-sectional study, and 3 case series on polydipsia and antipsychotics.
This systematic review aimed to elucidate the relationship between polydipsia and antipsychotics.
We systematically searched MEDLINE, Embase, and PsycINFO, and included clinical studies and case reports on polydipsia induced or improved by antipsychotics.
We identified 61 articles: 1 double-blind randomized controlled trial (RCT), 4 single-arm trials, 1 cross-sectional study, 3 case series, and 52 case reports. The double-blind RCT demonstrated no significant difference in improvement in polydipsia between olanzapine and haloperidol. Two single-arm trials showed that polydipsia improved during clozapine treatment, whereas the other 2 showed that risperidone did not improve polydipsia. The cross-sectional study showed the prevalence of hyponatremia with first-generation antipsychotics (FGAs: 26.1%) and second-generation antipsychotics (SGAs: 4.9%). Two case series reported that clozapine improved polydipsia; the other one indicated that patients with polydipsia who were treated with FGAs had schizophrenia (70.4%) and mental retardation (25.9%). Of 90 cases in the case reports, 67 (75.3%) were diagnosed with schizophrenia. Of 83 cases in which antipsychotic treatment started before the onset of polydipsia, 75 (90.3%) received FGAs, particularly haloperidol (n = 24, 28.9%), and 11 (13.3%) received risperidone. Among 40 cases in which polydipsia was improved following antipsychotic treatment, 36 (90.0%) received SGAs, primarily clozapine (n = 14, 35.0%).
Although the causal relationship between polydipsia and antipsychotics remains unclear because of the paucity of high-quality studies, antipsychotics with high affinity to dopamine D₂ receptors may be associated with an increased risk of polydipsia while clozapine may be effective for treating polydipsia.
Bionanocomposite systems based on montmorillonite and biopolymers for the controlled release of olanzapine
2017, Materials Science and Engineering C
Citation Excerpt :
OLZ has high permeability in biological membranes but low solubility in aqueous media, thus belonging to Class II according to the Biopharmaceutical Classification System [5,6]. Low water solubility increases the difficulty of dissolution and absorption of drug substances in the body, which affects the treatment of diseases [7] and has even been shown to contribute to fatal intoxication in the body [8]. Generally, oral administration affects the amount of available drug that accesses the systemic circulation after passing through the hepatic system (first pass effect).
Olanzapine (OLZ) is a drug that is used in the treatment of schizophrenia and other psychoses, and it belongs to the thienobenzodiazepine class. The OLZ molecule has low solubility decreasing bioavailability, but has high permeability in membrane biological being classified as a Class II drug substance according to the Biopharmaceutics Classification System. It was reported many side effects of administering OLZ orally. So, in order to increase the bioavailability of drug and possibly reducing some of side effects, this paper proposes a new material able to controllably release the drug in the body. To control the dissolution rate, this work proposes a system that incorporates the drug into montmorillonite (MMT) dispersed in a mixture of alginate (ALG) and xanthan gum (XG) biopolymers. The proposed hybrids and bionanocomposites were characterized by several physicochemical techniques, including XRD, IR-ATR, TG
DTA, SEM-EDS and HPLC. The characterization data confirmed the intercalation of the OLZ into the MMT by the ion exchange process, as well as the interaction of the MMT-OLZ with the biopolymers. The release test, conducted under various pH conditions, showed that the proposed system exhibited a more controlled drug release than commercial tablets, indicating that the ALG-XG/MMT-OLZ bionanocomposite can act as a controlled release system for OLZ.
An autopsy case of fatal water intoxication with postmortem computed tomography findings of diluted intestinal content and hemodilution
2016, Journal of Forensic Radiology and Imaging
Citation Excerpt :
In addition, no specific pathognomonic tissue changes establish death from water intoxication [8], which makes a postmortem diagnosis of water intoxication difficult. The vitreous humor is presumed to be more available for postmortem biochemistry analysis, because there are fewer postmortem influences [10,11]; however, the vitreous humor is not always sampled in daily forensic practice. Recently, the role of postmortem computed tomography (PMCT) as an adjunct to conventional autopsy has been well documented [12], although only clinical cases and animal models have been reported in terms of water intoxication [13,14].
No specific pathognomonic tissue changes establish death from water intoxication, which makes a postmortem diagnosis of water intoxication difficult. We report an autopsy case of fatal water intoxication in which the postmortem computed tomography (PMCT) examination showed findings suggestive of antemortem excessive water drinking, such as diluted intestinal contents and hemodilution. A 52-year-old man who had schizophrenia was found dead in his house. He frequently complained of polydipsia, and drank a large amount of water and vomited before his death. PMCT findings showed distention of the duodenum with low radiodensity content (7 HU). In addition, the right atrium showed a low radiodensity content (46 HU). Autopsy results showed moderate congestion in all the organs, a large amount of light-brownish liquid in the duodenum and upper jejunum, and aspiration pneumonia. Electrolyte concentrations of sodium in the vitreous humor of the right and left eyes were 105 and 107 mEq/L, respectively, and neither drugs nor alcohol was detected in the blood. On the basis of the autopsy and biochemical findings, we determined water intoxication as the cause of death. An evaluation of PMCT findings of cases of various causes of death indicated that the radiodensities of the right atrium and duodenal content in our case were lower than those of the cases of various causes of death, except for fresh water drowning. The present case showed that PMCT provides supplementary findings regarding antemortem excessive water drinking. In addition, PMCT may provide findings to consider death from water intoxication before autopsy.
Antipsychotic Drugs
2015, Side Effects of Drugs Annual
Citation Excerpt :
A study found that patients with SULT4A1-1-positive status experienced significantly less weight gain [186c]. A case of a male in his twenties on olanzapine who died of hyponatremia associated with water intoxication and high serum levels of olanzapine (610 ng/mL) is reported [187]. Two cases of postinjection delirium/sedation syndrome are reported [188A], including a 46-year-old male 4 hours post injection [189A].
The Side Effects of Drugs Annuals is a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of publications on adverse reactions to antipsychotic drugs from July 2013 to December 2014 covers amisulpride, aripiprazole, asenapine, blonanserin, chlorpromazine, chlorprothixene, clozapine, cyamemazine, droperidol, fluphenazine, haloperidol, iloperidone, levomepromazine (methotrimeprazine), loxapine, lurasidone, olanzapine, paliperidone, perazine, perospirone, perphenazine, pimozide, prochlorperazine, quetiapine, risperidone, sertindole, sulpiride, thioridazine, ziprasidone, zotepine, and zuclopenthixol.
Comparison of lithium levels between suicide and non-suicide fatalities: Cross-sectional study
2022, Translational Psychiatry

View all citing articles on Scopus

View full text

Case reportFatal water intoxication during olanzapine treatment: A case report

Abstract

Introduction

Section snippets

Case report

Cadaveric study

Results

Discussion

Conclusion

Schizophr Res

Forensic Sci Int

Biol Psychiatry

Ann Emerg Med

Forensic Sci Int

Olanzapine

Nihon Rinsho

Guidelines for screening and monitoring of cardiometabolic risk in schizophrenia: systematic evaluation

Br J Psychiatry

The atypical antipsychotic olanzapine enhances ingestive behaviour in the rat: a preliminary study

J Psychopharmacol

Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats

Clin Exp Pharmacol Physiol

Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat

Psychopharmacology

Case report
Fatal water intoxication during olanzapine treatment: A case report