# 01 - Psychotropics in overdose

# Psychotropics in overdose

The Maudsley® Prescribing Guidelines in Psychiatry, Fifteenth Edition. David M. Taylor, 
Thomas R. E. Barnes and Allan H. Young. 
© 2025 David M. Taylor. Published 2025 by John Wiley & Sons Ltd.
Chapter 13
Psychotropics in overdose
Suicide attempts and suicidal gestures are frequently encountered in psychiatric and 
general practice, and psychotropic drugs are often taken in overdose (Table 13.1). This 
section gives brief details of the toxicity in overdose of commonly used psychotropics. 
It is intended to help guide drug choice in those thought to be at risk of suicide, to give 
some indication of safe quantities to prescribe and to help identify symptoms of overdose. This section gives no information on the treatment of psychotropic overdose and 
readers are directed to specialist poisons centres. In all cases of suspected overdose, 
urgent referral to acute medical facilities is, of course, strongly advised.
Psychotropic drugs in special 
conditions
Table 13.1  Psychotropic drugs in overdose.
Drug or drug group
Toxicity in 
overdose*
Smallest dose likely to 
cause death
Signs and symptoms of overdose
Antidepressants
Agomelatine1,2
Low
No deaths reported. In early trials, 
800mg was maximum tolerated 
dose. EU SPC reports no serious 
effects from 2.45g overdose. A 
mixed overdose of 7.5g caused only 
drowsiness and mild tachycardia.
Sedation, agitation, stomach pains, 
dizziness
Brexanolone3
Not known
No deaths reported. Two cases of 
accidental overdose due to pump 
malfunction.
Sudden loss of consciousness
(Continued )

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CHAPTER 13
Table 13.1  (Continued )
Drug or drug group
Toxicity in 
overdose*
Smallest dose likely to 
cause death
Signs and symptoms of overdose
Bupropion4–7
Moderate
Around 4.5g, although largest 
overdose of 15g was not fatal.3,8
Tachycardia, seizures, QRS 
prolongation, QT prolongation, 
arrhythmia. Agitation and toxic 
psychosis also reported. Fatal 
serotonin syndrome may occur if 
taken with venlafaxine.9
Dextromethorphan 
and bupropion3
Probably 
moderate
Unclear. Bupropion inhibits 
metabolism of the 
dextromethorphan which may 
result in more severe/persistent 
overdose.
Bupropion: as above 
Dextromethorphan: nausea, vomiting, 
stupor, coma, respiratory depression, 
seizures, tachycardia, hyperexcitability, 
toxic psychosis
Duloxetine10–13
Low
Unclear – no deaths from single 
overdose reported but involved in 
numerous mixed overdose deaths.
Drowsiness, bradycardia, hypotension 
May be asymptomatic
Esketamine14
Not known
Unclear. No deaths reported.
Predicted to mirror ketamine overdose 
including sedation, hypertension, 
tachycardia, respiratory depression.15
Ketamine16
Moderate
Iatrogenic overdoses of up to 
50mg/kg IV are not usually fatal if 
prompt treatment is given. 
Mechanical ventilation may be 
required. Illicit overdose is rarely 
fatal unless other drugs present.15
Sedation, respiratory depression, 
hypertension, tachycardia
Lofepramine17,18
Low
Unclear. Fatality unlikely if 
lofepramine taken alone.
Sedation, coma, tachycardia, 
hypotension
MAOIs17,19–21
(not moclobemide)
High
Phenelzine – 400mg
Tranylcypromine – 200mg
Tremor, weakness, confusion, 
sweating, tachycardia, hypertension
Mianserin22–24
Low
Unclear but probably more than 
1000mg. Fatality unlikely if 
mianserin taken alone.
Sedation, coma, hypotension, 
hypertension, tachycardia, possible 
QT prolongation
Mirtazapine4,25–28
Low
Fatality unlikely in overdose of 
mirtazapine alone. One death 
reported following overdose with 
990mg.29
Sedation. Even large overdose may be 
asymptomatic. Tachycardia/
hypertension sometimes seen. 
Agitation.
Moclobemide30,31
Low
Unclear, but probably more than 
8g. Fatality unlikely if moclobemide 
taken alone.
Vomiting, sedation, disorientation
Reboxetine4,32
Low
Not known. Fatality unlikely in 
overdose of reboxetine alone.
Sweating, tachycardia, changes in 
blood pressure
SSRIs18,33–36
Low
Unclear. Probably above 1–2g. 
Fatality unlikely if SSRI taken alone.
Vomiting, tremor, drowsiness, 
tachycardia, ST depression. Seizures and 
QT prolongation possible. Citalopram 
most toxic of SSRIs in overdose28,37 
(coma, seizures, arrhythmia); 
escitalopram is less toxic.38,39

Psychotropic drugs in special conditions
CHAPTER 13
Table 13.1  (Continued )
Drug or drug group
Toxicity in 
overdose*
Smallest dose likely to 
cause death
Signs and symptoms of overdose
Trazodone11,40–43
Low
Unclear but probably more than 
10g. Fatality unlikely in overdose of 
trazodone alone. Mortality rate 
about 1 in 10,000 overdose 
exposures.28
Drowsiness, nausea, hypotension, 
dizziness. Rarely QT prolongation, 
arrhythmia.
Tricyclics17,19,20,44
(not lofepramine)
High
Around 500mg. Doses over 
50mg/kg usually fatal.
Sedation, coma, tachycardia, 
arrhythmia (QRS, QT prolongation), 
hypotension, seizures
Venlafaxine4,45–48
(desvenlafaxine 
causes similar effects 
but may be less 
toxic49)
Moderate
Probably above 5g, but seizures 
may occur after ingestion of 1g
Vomiting, sedation, tachycardia, 
hypertension, seizures, acidosis, 
hypoglycaemia. Rarely QT 
prolongation, arrhythmia, 
rhabdomyolysis. Very rarely cardiac 
arrest/MI, heart failure.
Vilazodone50,51
Low
Doses below 300mg are not fatal. 
No fatalities recorded in 714 
overdose exposures.28
Drowsiness, agitation, vomiting, 
seizures
Vortioxetine52
Low
Unclear. An overdose of 250mg 
caused no symptoms.
Nausea, somnolence, diarrhoea, 
pruritis
Antipsychotics
Amisulpride53–55
Moderate
Around 16g
QT prolongation, arrhythmia, cardiac 
arrest
Aripiprazole56–58
Low
Unclear. Fatality unlikely when 
taken alone.
Sedation, lethargy, GI disturbance, 
drooling
Asenapine59
Probably 
low
Unclear. No deaths from overdose 
reported. Oral absorption very 
limited.
Sedation, confusion, facial dystonia, 
benign ECG changes
Brexpiprazole3
Probably 
low
No information available
Presumably agitation and nausea
Butyrophenones60–62
(e.g. haloperidol)
Moderate
Haloperidol – probably above 
500mg. Arrhythmia may occur at 
300mg.
Sedation, coma, dystonia, NMS, QT 
prolongation, arrhythmia
Cariprazine63
Low
EU SPC reports one (non-­fatal) 
overdose of 48mg
Sedation, low blood pressure
Clozapine64,65
Moderate
Around 2g, but very much lower in 
those not tolerant to its effects66
Lethargy, coma, tachycardia, 
hypotension, hypersalivation, 
pneumonia, seizures
Iloperidone67–69
Probably 
moderate
Unclear but probably more than 
500mg.
Potent effect on QT interval. 
Sedation, tachycardia, respiratory 
depression, hypotension likely
Lumateperone70
Probably 
low
No overdoses reported
Presumably sedation and dizziness
(Continued )

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CHAPTER 13
Table 13.1  (Continued)
Drug or drug group
Toxicity in 
overdose*
Smallest dose likely to 
cause death
Signs and symptoms of overdose
Lurasidone71
Low
Unclear. An overdose of 1360mg 
was not fatal.72 One study reported 
no deaths in 821 overdose 
exposures.28
Very limited information. Minimal 
effect on QT interval.
Olanzapine64,73–76
Moderate
Unclear. Fatal outcomes have been 
reported for acute overdoses as low 
as 450mg.
Lethargy, confusion, myoclonus, 
myopathy, hypotension, tachycardia, 
delirium. Possibly QT prolongation.
Olanzapine and 
samidorphan3
Moderate
Unclear. An overdose of 
110mg/110mg was not fatal. 
Possible altered risk of fatality in 
opioid overdose due to opioid 
blockade.
As for olanzapine
Phenothiazines60,77–79
(e.g. chlorpromazine, 
fluphenazine)
Moderate
Chlorpromazine 5–10g
Sedation, coma, tachycardia, 
arrhythmia, pulmonary oedema, 
hypotension, QT prolongation, 
seizures, dystonia, NMS
Pimavanserin80
Not known
No overdoses reported but 
pimavanserin prolongs QT interval 
in clinical doses.
Probably QT prolongation and 
arrhythmia. ?Nausea, vomiting, 
confusion.81
Quetiapine28,64,82,83
Moderate
Unclear. Probably more than 5g. 
Fatalities can occur in single 
substance overdose.
Lethargy, delirium, tachycardia, QT 
prolongation, respiratory depression, 
hypotension, rhabdomyolysis, NMS
Risperidone64,84,85
(assume the same for 
paliperidone)
Low
Unclear. Fatality rare in those taking 
risperidone or paliperidone alone.
Lethargy, dystonia, tachycardia, 
changes in blood pressure, QT 
prolongation. Renal failure with 
paliperidone.
Ziprasidone86–91
Low
Around 10g. Fatality unlikely when 
taken alone.
Drowsiness, lethargy, QT 
prolongation, Torsades de pointes
Mood stabilisers
Carbamazepine92–94
Moderate
Around 20g, but seizures may 
occur at around 5g; an overdose of 
44g was not fatal.
Somnolence, coma, respiratory 
depression, ataxia, seizures, 
tachycardia, arrhythmia, electrolyte 
disturbance
Lamotrigine95,96
Low
At least 4g. Two deaths reported – 
one after 4g, the other after 7.5g, 
but overdoses of >40g have not 
proved fatal.
Drowsiness, vomiting, ataxia, seizures, 
tachycardia, dyskinesia, QT 
prolongation
Lithium97–99
Moderate
Chronic toxicity probably more 
dangerous but single overdose is 
occasionally fatal. Six acute 
overdose deaths recorded in UK 
2005–2012.100
Nausea, diarrhoea, tremor, confusion, 
weakness, lethargy, seizures, coma, 
cardiovascular collapse, bradycardia, 
arrhythmia, heart block, renal failure
Valproate101–105
Moderate
Unclear but probably more than 
20g. Doses over 400mg/kg cause 
severe toxicity.
Somnolence, coma, cerebral oedema, 
respiratory depression, blood 
dyscrasia, hypotension, hypothermia, 
seizures, electrolyte disturbance 
(hyperammonaemia)

Psychotropic drugs in special conditions
CHAPTER 13
Table 13.1  (Continued)
Drug or drug group
Toxicity in 
overdose*
Smallest dose likely to 
cause death
Signs and symptoms of overdose
Others
Benzodiazepines106–108
Low
Probably more than 100mg 
diazepam equivalents. Often 
involved in fatal mixed overdose 
but can be fatal when taken alone. 
Alprazolam is most toxic.
Drowsiness, ataxia, nystagmus, 
respiratory dysarthria, depression, 
coma
Buspirone28
Low
Limited data. Deaths not reported.
Not known
Daridorexant3
Not known
No overdoses reported. In trials, 
200mg was maximum dose.
Not known. Likely increased 
somnolence, muscle weakness, 
cataplexy-­like symptoms, headache.
Lemborexant3
Not known
No overdoses reported. In trials, 
75mg was maximum dose.
Not known. Likely increased 
somnolence.
Methadone109–111
High
20–50mg may be fatal in 
non-­users. Co-­ingestion of 
benzodiazepines increases toxicity.
Drowsiness, nausea, hypotension, 
respiratory depression, coma, 
pulmonary oedema, constricted 
pupils, rhabdomyolysis
Modafinil112–114
Low
Unclear, but no fatalities reported. 
Overdoses of >6g have not caused 
death.
Tachycardia, insomnia, agitation, 
anxiety, nausea, hypertension, 
dystonia
Pitolisant115
Not known
No overdoses reported. In trials, 
216mg was maximum dose.
Probably QT prolongation, headache, 
insomnia, irritability, nausea, 
abdominal pain
Pregabalin116–118
Low
Often involved in fatal mixed 
overdose (e.g. with opiates) but can 
be fatal when taken alone. One 
overdose of 8.4g caused 
unconsciousness and coma.
May be asymptomatic. Sedation and 
coma may occur
Solriamfetol3
Not known
No overdoses reported. In trials, 
1200mg was maximum dose.
Probably hypertension, tachycardia, 
QT prolongation
Suvorexant114,119
Low
Unclear. No deaths reported. An 
overdose of 100mg caused 
enhanced sedation.
Sedation, vomiting
Zolpidem120–122
Low
Unclear. Probably >200mg, but an 
overdose of 9g was not fatal. 
Fatality rare in those taking 
zolpidem alone.
Drowsiness, agitation, respiratory 
depression, tachycardia, coma, absent 
brainstem reflexes
Zopiclone106,123,124
Low
Unclear. Probably >100mg. Fatality 
rare in those taking zopiclone alone.
Ataxia, nausea, diplopia, drowsiness, 
coma
* High = less than 1 week’s supply likely to cause serious toxicity or death.
Moderate = 1–4 weeks’ supply likely to cause serious toxicity or death.
Low = death or serious toxicity unlikely even if more than 1 month’s supply taken.
GI, gastrointestinal; IV, intravenous; MAOIs, monoamine oxidase inhibitors; MI, myocardial infarction; 
NMS, neuroleptic malignant syndrome; SPC, summary of product characteristics.