Multiple drug ingestion for suicidal purpose alprazolam, citalopram.fh1
Multiple Drug Ingestion For Suicidal Purpose: Alprazolam,
Citalopram, Risperidone, Oxcarbazepine And Alcohol
Ýntihar Amacý Ýle Çoklu Ýlaç Ýçilmesi:
Alprazolam, Citalopram, Risperidone, Oxcarbazepine Ve Alkol
Yrd.Doç.Dr. Ayþe MIZRAK1, Yrd.Doç.Dr. Senem KORUK1, Ögr. Gör. Rauf GÜL1
Doç.Dr. Süleyman GANÝDAÐLI1, Prof.Dr. Ünsal ÖNER1
Doç.Dr. Aynur AKIN2, Prof.Dr. Aliye ESMAOÐLU2
1Gaziantep University Medical School Department of Anesthesiology and Reanimation
2Erciyes University Medical School Department of Anesthesiology and Reanimation
Hipnotik ajanlar, antidepresan ve antipsikotik ilaçlar uykusuzluk, depresyon ve psikotik hastalýklarýn tedavisinde yaygýn olarak kullanýlmaktadýr. Bu ajanlarýn aþýrý
dozda alýmýnýn rapor edilmesi giderek artmasýna raðmen alprazolam, citalopram, risperidone, oxcarbazepine ve alkolün hep birlikte alýmýný kapsayan bir vaka þu ana
kadar gösterilmemiþtir. Geliþmekte olan ülkelerde bu ilaçlarýn reçete edilmesi artmaya devam ettiði için bu ilaçlarýn klinik toksisitelerini ve klinik yaklaþýmlarýný
deðerlendirmek gereklidir. Biz, intihar amacý ile aþýrý dozda alprazolam, citalopram, risperidone, oxcarbazepine ve alkol alan ve destek tedavisi ile iyileþen 20 yaþýnda
bir kadýn olguyu bildirdik. Kadýn hastanýn yüksek dozda alprazolam (18 mg), citolapram hydrobromur (80 mg), risperidone (16 mg), oxcarbazepine (600 mg) ve ayný
zamanda alkol aldýðý ev arkadaþý ve uyanýk iken kendisi tarafýndan bildirilmiþtir. Hastaya standart detoksifikasyon prosedürü ve destek tedavisi uygulandý.
Alprazolam, citalopram, risperidone, oxcarbazepine, alkol, çoklu ilaç zehirlenmesi
Hypnotic agents, antidepressant and antipsychotic drugs are commonly used for the treatment of sleeplessness, depression, and psychotic disorders. Although
overdose intake with these agents is increasingly being reported, no case of co-ingestion including alprazolam, citalopram, risperidone, oxcarbazepine and alcohol has
been demonstrated so far. As prescription of these drugs continues to increase in developing countries, it is necessary to evaluate their clinical toxicity and clinical
approach. We reported a case of overdose with alprazolam, citalopram, risperidone, oxcarbazepine and alcohol in a 20-year-old female for suicidal purpose who recovered
with supportive management. It was reported by her room-mate and patient when conscious that she had taken high doses of alprazolam (18 mg), citolapram hydrobromur
(80 mg), risperidone (16 mg), oxcarbazepine (600 mg) and alcohol also. She was managed with standard detoxification procedures and supportive treatment.
Alprazolam, citalopram, risperidone, oxcarbazepine, alcohol, multiple drug intoxication.
Gaziantep Týp Dergisi 2008, 14:50-52.
Among young people, poisoning is a leading cause of
Many variable medication combinations may be used in
injury mortality in the United States. One of the major causes
a suicidal attempt. Most commonly we see one or two kinds
of death is a suicidal attempt. It is commonly seen in patients
of drugs taken. We mentioned here is a patient under
who take antidepressant medications (1). Prevention and
antidepressant treatment who taken multiple drug combinations
management of such overdose are of increasing clinical
which are not seriously toxic if taken alone but may have be
relevance as prescription of these kinds of drugs continues to
severe toxic effects when taken together. Each drug has a
increase (2). Though, little is known about these drugs (3),
central nervous system (CNS) depressant effect. First of them
several cases reported about overdose of these agents (4-7).
is alprazolam (an antidepressant), the second one is risperidone
(a type of phenothiazines), third one is citalopram hydrobromur
(a selective serotonine reuptake inhibitorSSRI), fourth one
is oxcarbazepine (an anticonvulsant and hypnotic agent) and
There is a lack of knowledge in the literature about the
Gaziantep Üniversitesi Anestezi ve Reanimasyon AD
Adres: Gaziantep Üniversitesi Týp Fakültesi
management of multiple drug ingestion in emergency and
intensive care unit. The treatment was effective because of
the rapidly introducing of patient to the hospital, emergent
evaluation and routine medications done immediately. It is
aimed to discuss a case of intoxication with the multiple drugs;
all of them were almost depressants of CNS.
Gaziantep Týp Dergisi 2008, 14:50-52.
Alprazolam has been shown to produce improvement in
patients with panic disorder (4). It has also been reported
A 20-year-old girl was taken to the emergency unit with
useful in alcohol withdrawal (5) and in some types of pain
an semi-unconscious situation. It was learned from her room-
mate and patient when conscious that she took high doses of
alprazolam (18 mg), citolapram hydrobromur (80 mg),
Although alcohol increases simple reaction it has much
risperidone (16 mg), oxcarbazepine (600 mg) and alcohol
more effect on central activity at this dose. Combination of
approximately 90 minutes before being admitted to the
benzodiazepines and alcohol has more effect on tests of motor
function and coordination than would be predicted from the
sum of the single effects and that alcohol is the dominant
On the initial examination she had a heart rate of 150
beats/min, respiratory rate of 22 breaths/ min. Body temperature
was 36.8 C. Systemic blood pressure was 90/50 mm Hg. Pupils
Patients receiving psychotropic medications are often
were mydriatic and positive to light reflexes. She was semi-
cautioned against the use of ethanol. 2 mg alprazolam in
conscious and Glasgow Coma Scale Score was 9. Her arterial
combinations with ethanol produced additive decrements in
blood gas analysis showed metabolic acidosis with a-13.5 base
performance on all cognitive and psychomotor tasks (8).
excess, and PaO2 87 mm Hg, PaCO2 52 mm Hg and SpO2
Benzodiazepines and ethanol may act partially on the same
80%. She was administered 100% oxygen via the face mask.
receptor; the lack of the interaction may be due in part to acute
In the pulmonary examination, wheezing was auscultated in
the basal zones. For the radiological assessment, chest X-ray
examination was applied and it showed a pneumonic infiltration
In our case chemical causes of CNS depression were
which was thought to be a pulmonary aspiration in the lung.
alprazolam (Xanax), risperidone (Risperdal), citalopram
hydrobromur (Cipram), oxcarbazepine (Trileptal) and alcohol.
Pulmonary aspiration may have happened while vomiting
She wasnt tolerant to the effect of that dose alcohol. Although
before transfered to hospital. Blood glucose level was 75
doses of all drugs ingested were not toxic level, their doses
mg/dl. Serum CPK enzyme level was normal.
higher than their therapeutic doses. Their combination resulted
Electrocardiogram showed negative T waves in the V2 and
in clinical toxicity. This may be due additive or potential effects
V3 derivations. It was thought to be the result of co-ingestion
of drugs ingested together. These drugs have a potential of
of these drugs . In order to exclude an intracranial pathology,
cranial CT scan was performed and was reported as normal.
Risperidone (Risperdal) (a phenotiazine) is used for its
As she was not unconscious completely and was able to
antiemetic, antipsychotic and sometimes analgesic and hypnotic
obey our commands, gastric lavage was performed via a naso-
effects. Serious symptoms may be occur after 1mg/kg dose.
gastric catheter of 14 G. As the aspiration material was not
Higher doses can cause liver injury, cirrhosis, and
enough, we decided to give 50 grams of active charcoal and
agranulocytosis. Risperidone toxicity manifests primarily with
laxafenol (300 mg, 2x1) via the naso-gastric catheter in the
mild central nervous system effects and reversible
supine-sitting position. It was repeated for every six hours.
neuromuscular and cardiovascular effects (11).
Flumazenil, the antagonist of alprazolam, was given in titrated
doses of 0.5 mg intravenously. For supportive treatment fluid
Citalopram hydrobromur (Cipram) is a selective serotonin
replacement therapy, antibiotics (seftriaxone;1 grX1,
reuptake inhibitor drug and may be efficacious in the treatment
clindamycine;600 mg, 1X1), gastric acid inhibitor agent
of depression, senile dementia, alcohol withdrawal syndrome
(ranitidine, 150 mg X2), bronchodilator agents and n-acetyl
and bipolar disorder. Minimum lethal level of its blood
cystein (Asist; 4X1) applied in routine doses.
concentration was reported 5200 mg. After using with other
CNS depressant agent risk of arrhythmia and convulsion
After six hours from the beginning of the treatment she
increases. Acute toxicity with this drug results in
became conscious completely and orally cooperated. Blood
rhabdomyolysis, renal failure, hypoxia and seizures (12).
pressure was improved and arterial oxygen saturation increased
to 81% at the sixth and 96% at the twelfth hours. T waves in
Oxcarbazepine (Trileptal) has an anticonvulsant and
the V2 and V3 derivations and other abnormal parameters
hypnotic effect via CNS depressant effect. Overuse causes
returned to normal in 48 hours. Oral feeding was begun on
respiratory insufficiency and coma. There is no antidote agent
the second day and she referred to psychiatry clinic on the
to use in oxcarbazepine toxicity (13).
Flumazenil is a benzodiazepine antagonist and can be used
in addition to supportive care at iv doses of 0.01 mg/kg. It
binds to the benzodiazepine receptor, where it competitively
displaces benzodiazepines and reverses sedative and anxiolytic
Alprazolam is a triazolobenzodiazepine that appears both
effects (14). It reverses sedation, respiratory depression,
to exhibit a high affinity for BZ receptors and activate brain
amnesia and psychomotor effects of benzodiazepines (e.g.,
a2-adrenoceptors. Because it acts as benzodiazepine and a2-
midazolam, alprazolam, diazepam, flurazepam, lorazepam)
drenoceptor agonist also it may be particularly efficacious in
(15). Flumazenil only has a 1 hour half-life and may need to
the treatment of the alcohol withdrawal syndrome (1).
Gaziantep Týp Dergisi 2008, 14:50-52.
In this case use of alprazolam, ethanol, Risperidone,
5.Kolin IS, Linet QT. Double-blind comparison of the anxiolytic
citalopram and Oxcarbazepine together and in overdoses
efficacy of alprazolam and chlordiazepoxide hydrochloride in
produced syncope, hypotension, tachycardia, metabolic acidosis,
the chronic withdrawal period from alcohol. Curr Ther Res.
Our goal in treating those drugs overdoses was to prevent
6.Fernandez F, Adams F, Holms VF. Analgesic effect of
hypotension and severe CNS depression. Gastric lavage was
alprazolam in patients with chronic, organic pain of malignant
performed and activated charcoal was given for the ingestion
of large doses. If the patient had been unconscious we wouldnt
perform gastric lavage because of the aspiration possibility.
7.Sellers EM, Busto U. Benzodiazepines and alcohol:
Rajkumar et al. Reported an other multi-drug overdose and
Assessment of the effects and consequences of psychotropic
they intubated the unconscious patient without performing
drug interactions. J Clin Psychopharmacol. 1982;2:249-262.
gastric lavage and then they started the supportive treatment
(17). Heart rate, blood pressure, body temperature, and
8.Linnoila M, Stapleton JM, Lister R, Moss H, Lane E, Granger
respiration rates were monitorized. Intravenous fluid was
A. Effect of single doses of alprazolam and diazepam, alone
needed for prevention of hypotension. The unique antidote,
and in combination with ethanol, on psychomotor and cognitive
flumazenil, was used treating alprazolam overdose. However,
performance and on autonomic nervous system reactivity in
toxicity may be worsened by extremes of age (18), substance
healty volunteers. Eur J Clin Pharmacol. 1990;39:21-28.
abuse, medical co-morbidity, co-ingestion of other agents (2)
and obesity, our patient had none of these worsening factors
9.Palva ES, Linnoila M, Scario I, Mattila MJ. Acute and
and co-ingestion of alprazolam (18 mg), citolapram
subacute effects of diazepam on psychomotor skills: Interactions
hydrobromur (80 mg), risperidone (16 mg), oxcarbazepine
with alcohol. Acta Pharmacol Toxicol. 1979;45:257-264.
(600 mg) and alcohol didnt prove fatal. As multiple overdoses
may be common, our report provides an information regarding
10.Fu K, Konrad RJ, Hardy RW, Brisie RM, Robinson CA.
An unusual multiple drug intoxication case involving
It is rare to see a patient who had taken overdoses of these
citalopram. J Anal Toxicol. 2000;24(7):648-50.
kinds of drugs together. Probably the doses taken for each
drugs alone may not have toxic effects but when they are taken
11.Acri AA, Henretig FM. Effects of Risperidone in overdose.
together they have synergistic effects and cause severe toxicity.
12.Rothenhaeusler HB, Rothenhäusler HB, Hoberl C,
Ehrentrout S, Kapfhammer HP, Weber MM, et al Suicide
attempt by pure citalopram overdose causing longlasting severe
The multiple drug overdose reported here showed that
sinus bradycardia, hypotension and syncopes: successful
prompt supportive treatment, early detection of overdose, the
therapy with a temporary pacemaker. Pharmacopsychiatry.
rapid, correct and optimal management can provide a successful
13.Wong ICK, Lhatoo SD. Adverse reactions to new
anticonvulsant drugs. Drug Safety. 2000;23(1)35-36.
14.Haddad LM, Shannon MW, Winchester JF Clinical
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Saunders, Philadelphia. 1998;610-618.
1.Eriksson E, Carlsson M, Nilsson C, Soderpalm B. Does
15.Omoigui S. The Anesthesia Drugs Handbook 2 nd ed.
alprazolam, in contrast to diazepam, activate a
2 adrenoceptors Susan M Gay. USA 1995;134-137.
involved in the regulation of rat growth hormone secretion?
16.Lemke KA. Ability of flumazenil, butorphanol, and naloxone
to reverse the anesthetic effects of oxymorphone-diazepam in
2.Trenton A, Currier G, Zwemer F. Fatalities associated with
therapeutic use and overdose of atypical anti psychotics. CNS
17.Rajkumar AP, Jebaraj P, Tharyan P. Multi-drug overdose
risperidone, ziprasidone, valproate, trihexyphenidyl, and
3.Capel MM, ColbridgeMG, Henry JA. Overdose profiles of
new antipsychotic agents. Int J Neu. 2000;3:51-4.
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4.Charney DS, Woods SW, Boodman WK, Rifkin B, Kinch
medications in children: does newer necessarily mean safer?
M, Aiken B, et al. Drug treatment of panic disorder: The
comparative efficacy of imipramine, alprazolam, and trazodone.
Gaziantep Týp Dergisi 2008, 14:50-52.
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MD ACCOMPLISHMENTS HANAUER, STEPHEN B Dr. Hanauer received funds from CCFA from 1992 to 1995 to carry out a multicenter evaluation of the efficacy of methotrexate in chronically active CD. Methotrexate has been proven effective in moderate to severe CD (1) and to maintain remission in adults with CD (1,2). Hanauer participated in several studies evaluating its efficacy and safety, parti