Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management

Figures & data

Table 1. 1985–2003 TESS TCA deaths (single drug, unintentional)

Age/sex	TCA	Dose/serum concentration	Circumstances
13 mo/F	I	Empty bottle/unk time	Coma at home, cardiac arrest in ED, cerebral anoxia. Died 36 hr after admission.
18 mo/M	I	Whole bottle	30 mins to ED. Seizures, arrest, lavage, lorazepam, dopamine, NaHCO3. Hypotension, widened QRS 5 hr later, seizure, arrhythmias, died 27.5 hr after admission.
30 yr/F	I	Empty bottle	No pulse. DOA.
10 mo/F	De	600 mg	Coma at home; To ED 90 mins after ingestion. Lavaged, ventricular fibrillation, pH 6.9, CPR, dead within 1 hr.
11 mo/M	De	Possibly 1 tablet	ED by 1 hr. Ataxic, lavage, activated charcoal, seizure, arrest.
15 mo/M	De	500 mg 2556 ng/mL	Coma, hypotension. Intubated, ventilated, dopamine, NE, died 2nd d after admission.
19 mo/F	De	Unk dose/time1377 ng/mL	Seizure, cardiac arrest at home; pH 6.9; cerebral edema, ileus, diabetes insipidus, brain dead 4 d after admission. Multiple-dose activated charcoal, NaHCO3, epinephrine, isoproterenol, atropine, Fab, mannitol, furosemide, hyperventilated.
20 mo/M	De	800 mg1600 ng/mL	Seizure, hypotension, widened QRS. Within 2 hr of ED admission, 2 cardiac arrests and died. Phenytoin, NaHCO3, pacer, physostigmine.
20 mo/F	De	Unk dose	Seizure at home, skin grey, intubated, p = 60, DOA.
2 yr/F	De	1250 mg3900 ng/mL	Vomited at home, apnea, cardiac arrest in car, DOA.
2 yr/M	De	1250 mg8000 ng/mL	ED by 45 min. Seizure, bradycardia, arrest. ACLS, intubation/atropine, NE, pacing. Dead at 1 hr.
3 yr/M	Do	Unk dose/time	Coma, cardiac arrest at home. DOA.
5 yr/?	Do	900 mg	Therapeutic error? Vomited; found dead at home.
84 yr/M	Do	AOC: 200 mg	Coma, respiratory depression.
17 mo/M	A	Unk dose/time	Seizure, pneumothorax. NaHCO3, intubated, ventilation, dopamine, NE, diazepam. Died on 12^th d.
3 yr/M	A	100–125 mg	Cyanosis, coma, DOA
5 yr/M	A	Unk dose/timeA 1150 ng/mLN 790 ng/mL	DOA. Necrotizing pneumonia & pulmonary edema at autopsy.
5 yr/M	N	Unk dose851 ng/mL	Coma, hyperthermic, hypotensive, aspiration pneumonia, arrhythmias. Intubated, ventilated, lidocaine, NE, bretylium, NaHCO3, dopamine, antibiotics. Multisystem failure over 5 d.

ED: emergency department; Fab: Digoxin Fab anti-digoxin antibodies; CPR: cardiopulmonary resuscitation; AOC: acute on chronic; ACLS: advanced cardiac life support; DOA: dead on arrival at emergency department; NaHCO₃: sodium bicarbonate; NE: norepinephrine; Unk: unknown; TCA: I = imipramine, De = desipramine, A = amitriptyline, Do = doxepin, N = nortriptyline.

Table 2. Current formulations and dosing recommendations for tricyclic antidepressants (309–311)^†

Amitriptyline HCl tablets (Elavil^‡, Endep): 10, 25, 50, 75, 100, 150 mg

Adults: 40–100 mg initially and daily maintenance (max 150–300 mg daily)

Adolescents & elderly: 10 mg TID and 20 mg q HS (maximum: 200 mg daily)

Clomipramine HCl capsules (Anafranil): 25, 50, 75 mg

Adults: 25 mg initially to 100 mg maintenance (max 300 mg daily)

Children (10–18 years old): 25 mg initially to 100 mg (or 3mg/kg) maintenance (max 200 mg daily)

Desipramine HCl tablets (Norpramin): 10, 25, 50, 75, 100, 150 mg

Adults: 100–200 mg (max 300 mg daily in hospitalized patients)

Adolescents & elderly: 25–100 mg (max 150 mg daily)

Child (6–12 years old): 1–3 mg/kg/day (max 5 mg/kg/day)

Doxepin HCl capsules (Sinequan): 10, 25, 50, 75, 100, 150 mg; oral concentrate 10 mg (base)/ mL

Adults: 25–75 mg (max 300 mg daily – max single dose: 150 mg)

Child: 1–3 mg/kg/day

Doxepin cream (Prudoxin, Zonalon): 5%; each g = 50 mg doxepin HCl

As directed QID.

Imipramine HCl tablets (Norfranil, Tipramine, Impril, Janimine, Novopramine, Tofranil): 10, 25, 50 mg

Impiramine pamoate capsules (Tofranil-PM): 75, 100, 125, 150 mg

Adults: 75–100 mg daily (max 200 mg daily; 300 mg daily for hospitalized patients only)

Adolescents & elderly: 30–40 mg daily (max 100 mg daily)

Children: >5 yr of age 1.5–2.5 mg/kg/day (max 5 mg/kg/d)

Child (enuresis, in 6–12 years old): 25–50 mg at bedtime

Child (enuresis, in ≥12 year olds) 25–75 mg (max 2.5 mg/kg)

Nortriptyline HCl capsules (Aventyl, Pamelor): 10, 25, 50, 75 mg; oral concentrate 10 mg/5 mL

Adults: 25 mg TID or QID (max 150 mg daily)

Adolescents & elderly: 30–50 mg daily (max 50 mg daily)

Children 6–12 years old: 1–3 mg/kg/day or 10–20 mg/day

Protriptyline HCl tablets (Vivactil): 5, 10 mg

Adults: 15–40 mg daily in divided doses (max 60 mg daily)

Adolescents & elderly: 15 mg daily initially (max 20 mg daily)

Trimipramine maleate capsules (Surmontil): 25, 50, 100 mg

Adults: 75–100 mg in divided doses (max 150 mg outpatients; 200 mg hospitalized patients)

Adolescents & elderly: 50 mg daily (max 100 mg daily)

Tricyclic Antidepressants in Combination

Perphenazine & amitriptyline HCl tablets (Etrafon, Triavil): 2/10, 2/25, 4/10, 4/25, 4 mg/50 mg

Amitriptyline dosing same as above

Chlordiazepoxide & amitriptyline HCl tablets (Limbitrol): 5/12.5, 10 mg/ 25 mg

Amitriptyline dosing same as above

*Manufacturers specify to use their lower maximum doses in outpatient, unmonitored settings.

^†Manufacturers do not recommend most tricyclic antidepressants for use in children.

^‡Elavil is no longer marketed in the U.S.

Table 4. One-time overdoses of tricyclic antidepressants in children less than 6 years of age

Drug	Dose(mg/kg)	Age sex	Onset of symptoms	Duration of toxicity	Arrhythmia	Cardiac arrest	Coma	Hypotension	Pneumonia	Pulmonary edema	Respiratory arrest	Respiratory depression	Seizure	Fatal	Ref.
A	81	15 mo F	45 min	–	X			X			X		X	Yes	228
A^‡	68	24 mo F	–	–									X	No	42
A	36	23 mo M	–	–	X	X	X	X			X	X	X	No	197
A^‡	31	24 mo F	<60 min	–			X							No	229
A^‡	19	17 mo F	–	–			X							No	230
A	4	48 mo M	3.5 hr	24 hr										N	231
A	–	42 mo F	<180 min	24 hr	X									No	232
A	–	36 mo M	240 min	–	X		X	X						No	151
A SR^§	–	60 mo M	–	–										No	233
N	16	48 mo	–	–										No	48
N	–	30 mo M	<120 min	–	X		X	X					X	No	232
I	213	24 mo M	–	–		X	X				X			Yes	163
I	188	30 mo M	60 min	Several d	X		X	X					X	No	173
I	155	30 mo M	10 min	^–		X	X				X		X	Yes	234
I	116	35 mo M	30 min	2–3 d	X	X	X	X			X		X	No	235
I	100	20 mo M	40 min	–	X		X	X					X	No	236
I	90	19 mo M	<45 min	48 hr	X			X					X	No	237
I	86	36 mo M	–	–	X	X	X	X			X			Yes	238
I	70	? M	105 min	–	X		X	X					X	No	42
I	68	30 mo M	<14 hr	–	X		X	X					X	No	236
I	62	30 mo M	3.5 hr	Several d	X		X	X			X		X	No	239
I	61	48 mo F	–	–										No	240
I	57	24 mo F	30 min	–	X		X	X			X		X	Yes	241
I	60	30 mo F	–	5 d	X		X	X					X	No	232
I	47	36 mo F	–	2 d	X		X	X					X	No	242
I	47	30 mo	–	–										Yes	243
I	44	18 mo F	–	–	X		X				X			Yes	244
I	40	23 mo M	<90 min	2 d	X		X	X			X		X	No	245
I	36	44 mo M	–	2–3 d	X		X			X		X	X	No	246
I	50	20 mo M	<180 min	–	X									No	232
I	34	22 mo M	<120 min	24 hr	X			X					X	No	247
I	32	48 mo M	240 min	–		X	X						X	Yes	150
I	31	30 mo M	30 min	Several d	X	X	X	X					X	No	248
I	31	30 mo M	15 min	–	X	X	X	X			X		X	Yes	249
I	30	18 mo F	75 min	–	X		X	X					X	No	44
I	26	36 mo F	<60 min	4 d	X		X		X			X	X	No	221
I	26	20 mo	–	–	X		X						X	No	250
I	25	30 mo M	120 min	>13 hr			X							No	251
I	25	18 mo M	90 min	–	X		X	X					X	Yes	50
I	25	14 mo F	–	–	X		X	X	X		X		X	Yes	196
I	25	11 mo M	30 min	–	X	X	X	X					X	Yes	198
I	23	26 mo F	30 min	–	X		X	X	X		X		X	No	252
I	23	18 mo F	90 min	7 d	X		X	X				X	X	No	253
I	21	21 mo F	–	–									X	No	254
I	20	15 mo F	–	–	X		X						X	Yes	62
I	15	30 mo	240 min	–	X	X	X				X	X	X		38
I	12	36 mo F	–	–		X							X	No	42
I	8	30 mo	–	–	X								X	No	254
I	7.5	15 mo M	120 min	–	X			X					X	No	50
I	5	19 mo M	75 min	24 hr			X							No	50
I^†	3	60 mo M	<60 min	48 hr			X							No	50
I	^–	24 mo M	6 hr	Several d			X						X	No	50
I	^–	24 mo F	180 min	12 hr	X		X						X	No	255
I	^–	16 mo F	?	–			X							Yes	256
I	^–	15 mo M	–	–	X		X						X	No	205
De	171	24 mo F	<60 min	–	X		X	X	X				X	Yes	257
De	65	19 mo M	90 min	28 hr	X		X				X	X	X	No	214
De	30	19 mo F	–	–	X		X						X	Yes	44
De	6	15 mo	–	–											49

*Italics indicate estimated dose from the child's weight at 95^th percentile for age.

^†Co-ingestant thioridazine.

A = amitriptyline.

A-SR = amitriptyline, sustained release.

^‡Co-ingestant perphenazine.

N = nortriptyline.

De = desipramine.

^§Co-ingestant orphenadrine.

I = imipramine.

Table 3. Comparison of poison center guidance: tricyclic antidepressants, May, 2004

Poison center	A	B	C	D	E	F	G	H	I
Stay-home dose (child)	≤5 mg/kg	<5 mg/kg	—	one pill	<3 mg/kg	<5 mg/kg	—	Rx dose (≤6 yr), double dose (7–64 yr)	<3.5 mg/kg
Protriptyline						<1 mg/kg
Follow-up calls	1–2, 6 hr	1–2, 4–6 hr, prn	—	—	2, 6 hr	—	—	2, 4, 6 hr	2 hr
AC	Yes	Yes	Yes	Yes, remove pill fragments	Yes	Yes	Yes	Yes	Yes
Multi-dose AC	—	No	No	Yes	Yes	—	No	Yes	—
Lavage	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Ipecac	—	No	—	No	—	Not preferred	No	—	No
NaHCO3 bolus	—	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
NaHCO3 drip	—	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Target blood pH			7.45–7.50	7.45–7.55	7.45–7.55	7.45–7.55	7.45–7.50	7.45–7.55	<7.55
Symptoms monitored at home	Minor drowsiness	No	—	No	Minor drowsiness	—	—	Minor drowsiness, urinary retention	No

Legend: prn = as needed, AC = activated charcoal, NaHCO₃ = sodium bicarbonate, Rx = therapeutic.

Table 5. One-time overdoses of tricyclic antidepressants in patients 6 years of age and older

Drug	Dose (mg)	Age (yr) sex	Onset (hr)	Duration	Survived	Ref.
A	10,000	32 F	–	–	Yes	251
A	9000	46 F	1	Several d	Yes	258
A	8000	45 M	–	–	Yes	219
A	6300	30 F	–	–	No	259
A	6000	38 M	–	7 d	Yes	260
A^†	6000	35 F	–	–	Yes	204
A	6000	29 M	1	–	Yes	261
A	5000	30 F	–	5 d	Yes	260
A	3750	23 M	2.5	–	Yes	262
A	3750	25 F	3	3 d	Yes	263
A	3000	36 M	–	2 d	Yes	264
A	2750	31 F	–	–	Yes	265
A	2500	42 F	2	36 hr	Yes	266
A	2500	70 F	3	–	Yes	267
A	2200	57 M	–	16 mo	Yes	268
A	2000	26 F	–	–	No	269
A^†	2000	39 F	–	4 d	Yes	202
A	2000	47 M	–	2 d	Yes	270
A	1875	23 F	–	–	Yes	86
A	1750	19 F	–	–	Yes	271
A	1500	30 F	–	–	Yes	272
A	1500	38 M	–	–	Yes	86
A	1300	41 F	1	Several d	Yes	273
A	1250	– F	–	–	Yes	265
A^†	1250	25 M	–	–	No	274
A	1250	56 M	–	–	No	159
A	1200	42 M	–	–	Yes	275
A	1050	14 F	–	Several d	Yes	276
A	1050	17 M	–	–	Yes	93
A	1000	24 M	2	24 hr	Yes	277
A	1000	35 F	–	–	Yes	117
A	1000	61 M	9	–	Yes	278
A^†	1000	65 M	2	Several d	Yes	279
A	1000	67 M	4.5	48 hr	Yes	280
A	950	70 F	4.5	–	No	280
A	800	53 F	–	–	Yes	281
A	850	67 F	1	3.5 hr	No	3
A	750	14 M	–	–	Yes	230
A^†	750	44 M	16	Several d	Yes	155
A	750	45 F	–	13 d	No	259
A	525	8 M	–	–	Yes	229
A	500	45 F	3		Yes	262
A	350	33 F	–	–	Yes	117
A	300	22 F	–	36 hr	Yes	52
A	200	46 F	1	–	Yes	196
A	150	52 F	–	–	Yes	21
A	–	13 M	–	–	Yes	230
A	–	18 M	–	–	Yes	149
A	–	22 F	–	–	Yes	151
A	–	22 F	–	–	Yes	151
A	–	24 F	–	–	Yes	265
A	–	24 F	2	–	Yes	152
A	–	25 F	–	–	Yes	282
A	–	27 F	–	–	No	182
A	–	28 F	–	4 d	Yes	260
A	–	28 F	2	–	Yes	93
A	–	31 F	–	3 d	Yes	152
A	–	33 M	–	–	No	283
A	–	34 F	–	7 d	No	284
A	–	35 F	–	–	Yes	149
A	–	38 F	1	–	No	219
A	–	39 F	–	Several d	Yes	190
A	–	39 F	–	Several d	Yes	285
A	–	44 F	–	–	Yes	286
A	–	44 M	12	–	Yes	287
A^†	–	44 M	–	50 hr	No	92
A	–	46 F	2	56 hr	No	154
A	–	47 F	–	–	No	269
A	–	55 F	–	8 d	Yes	288
A	–	56 F	0.25	–	Yes	222
A	–	16 F	–	3 d	Yes	226
A	–	63 M	–	3 d	Yes	213
A/I	1000	9 F	–	2 wk	Yes	289
A/I	–	47 F	2	–	Yes	222
A/I	–	50 F	6	4 hr	Yes	290
A/N	–	34 F	3	40 hr	No	2
C	15,000	27 M	5	>4 d	Yes	66
C	750	48 F	6	2 weeks	Yes	22
De	9000	15 F	–	–	No	73
De	2700	14 F	–	–	Yes	75
De	2500	40 F	–	–	Yes	54
De	2000	24 F	4	–	Yes	69
De	1800	22M	7	19 hr	Yes	72
De	1500	38 F	2	–	No	68
De	1500	19 F	4	–	Yes	67
De	1200	18 F	12	–	Yes	70
De	1150	58 F	1.5	Several hr	Yes	74
De	–	19 F	–	–	Yes	189
De	–	31M	–	–	Yes	218
De	–	27 F	–	–	No	2
Do	3000	55 M	–	–	Yes	77
Do	2500	24 M	1	–	No	78
Do	1500	35 F	3	–	No	80
Do	1500	54 F	1	24 hr	Yes	81
Do	600	34 M	4	–	Yes	79
Do	–	18 F	2	–	No	152
Do	–	23 M	1	13 hr	No	82
Do	–	49 F	–		Yes	291
Do	–	53 F	–	–	Yes	117
I	10,000	34 F	–	–	No	54
I	5375	21 F	3.5	Several d	Yes	292
I	5350	23 F	1.5	–	Yes	171
I	4700	41M	–	Several d	Yes	293
I	4500	25 F	–	–	Yes	188
I	2500	30 F	–	–	Yes	294
I	2500	14 F	2	–	Yes	211
I	2250	19 F	0.66	Several d	Yes	295
I	1875	38 F	–	–	No	296
I	1500	14 F	–	–	Yes	199
I	1500	29 F	8	3 d	Yes	297
I	1250	19 F	0.75	–	Yes	209
I	1250	24 F	–	–	Yes	136
I	1150	38 F	2	–	Yes	298
I^†	1000	6 M	4	–	Yes	299
I^†	1000	8.5 M	–	–	No	300
I	1000	47 F	–	–	No	159
I^†	800	32 M	–	–	Yes	133
I	750	7 M	4	–	Yes	300
I	750	36 F	–	–	No	301
I^†	625	28 F	2	–	No	302
I	475	7 F	–	–	Yes	303
I	–	10 M	–	–	No	210
I	–	18 M	–	–	No	54
I	–	24 F	–	–	No	304
I	–	25 F	–	–	Yes	305
I	–	27 F	1.5	–	Yes	306
I	–	27 F	–	–	Yes	212
I	–	28 M	1	–	No	209
I	–	29 F	–	–	Yes	54
I	–	34 F	10	–	Yes	307
I	–	36 F	–	–	No	137
I	–	37 F	–	–	No	137
I	–	40 M	–	–	Yes	308
I	–	49 F	–	5 d	No	153
I	–	54 F	–	–	Yes	200
N	8000	29 F	0.25	–	Yes	90
N	5000	52 F	–	–	Yes	89
N	2350	69 F	2	10 hr	No	82
N	2000	30 F	–	17 hr	No	91
N^†	1250	21 F	–	–	No	92
N	1250	59 M	–	–	Yes	86
N	950	19 F	0.75	–	Yes	87
N	600	25 F	4	24 hr	Yes	85
N	–	16 F	–	–	No	88
N	–	34 F	–	–	No	151
P	–	28 M	–	–	No	201
T	3500	21 F	–	–	Yes	93
T	–	59 F	–	–	Yes	93
Unk	–	39 F	–	–	Yes	207
Unk	–	45 M	–	–	Yes	208

*Co-ingestant confirmed.

^†Acute-on-chronic poisoning.

A = amitriptyline.

C = clomipramine.

De = desipramine.

Do = doxepin.

I = imipramine.

N = nortriptyline.

P = protriptyline.

T = trimipramine.

Table

Grade of recommendation	Level of evidence	Description of study design
A	1a	Systematic review (with homogeneity) of randomized clinical trials
	1b	Individual randomized clinical trials (with narrow confidence interval)
	1c	All or none (all patients died before the drug became available, but some now survive on it; or when some patients died before the drug became available, but none now die on it.)
B	2a	Systematic review (with homogeneity) of cohort studies
	2b	Individual cohort study (including low quality randomized clinical trial)
	2c	“Outcomes” research
	3a	Systemic review (with homogeneity) of case-control studies
	3b	Individual case-control study
C	4	Case series, single case reports (and poor quality cohort and case control studies)
D	5	Expert opinion without explicit critical appraisal or based on physiology or bench research
Z	6	Abstracts

Table