Dr. Peter Chan, MD, FRCPC
Geriatric and Consult-Liaison Psychiatristand Head of ECT Program,
Vancouver General Hospital.Clinical Associate Professor, Dept. of Psychiatry,
University of British Columbia.
Learning Objectives
To review symptoms and signs of catatonia including lethal catatonia.
To know the overlap between catatonia and neuroleptic malignant syndrome.
To understand the role of ECT in both catatonia and neuroleptic malignant syndrome
Case Presentation-1: Ms. A 68 y.o. Italian independent woman, some
command of English, on Thioridazine (Mellaril) for 49 years, since last institutional admission.
History of Psychosis, postpartum. No family psychiatric history Brief hosp. In 1990’s at SVH after Thioridazine
briefly D/C’d...hysterectomy Widow in 2002, lives alone in house, Gr. 5
education, restaurant worker, supportive 2 sons,1 dtr., brother and sister
Case Presentation-2: Ms. A June 2007
Loxapine 25 mg bid after stop Mellaril in May 2007Labile, energetic, little sleep, racing thoughtsSmelling bad odours in homeParanoid, carrying knife, throwing items in frustration“Confused” , disorganized, suicidalVGH Inpt Unit via emergency (June 10-July 18)
○ Dx: Bipolar Disorder○ Olanzapine 15 mg qhs○ Trazadone 100 mg qhs○ Clonazepam 0.25 mg/d
Case Presentation-3: Ms. A Short-term Assessment and Treatment
(STAT) Geriatric In Unit (Aug 23, 2007)Had been seen at STAT DayprogramIncontinent with urinary retentionSwitched from Olanzapine to CPZ 250 mg/d
by community psych.Dependent on IADL’s3MS=72/100; FMMSE=24/29
Case Presentation-4: Ms. A STAT In-Unit (Aug 23-Sept 14)
Mood labile, insomniaAlternates between singing at night and
weeping in daytime, playing operaSome pressure of speech
○ Dx: Bipolar, mixed state○ Epival 750 mg/d○ Quetiapine 100 mg qhs
Case Presentation-5: Ms. A Sept 15-28, 2007: Home
Hypomanic in DayprogramIncreased home supportCompliant with Epival (level=498) , mixing up blister
packed meds?Son called emergency mental health services on Sept 25:
threaten him with a knife “leave me alone”, crying continually, plays loud opera music in the phone, looking for a new partner, hostile and throwing things, isolate from family
Quetiapine up to 175 mg/d
Case Presentation-6: Ms. A VGH Psych Emerg. and STAT (Sept 28-Nov 5)
Seroquel increased to 350 mg/d, multiple IM doses in Psych Emerg. Seclusion room.
Oct 3: ○ Mood labile○ Demanded to see her husband, anniversary party○ Sad...join husband, tearful, tangential, speak loud○ Physically aggressive○ Grandiose “I’m God. Don’t touch me...kill you”○ Sleeping 2 hrs.○ 3MS=49/100; FMMSE=18/30○ Clonazepam 2 mg/d, Seroquel, Epival (level = 571)
Case Presentation-7: Ms. A
Oct 31:Feel dizzy, speech different, tremor, headacheCPK=37, WBC=8000, Valproic level=660
Nov 2:3 hrs/nt sleep past 2 ntsParanoid, hypervigilantFine resting tremor (no cogwheeling)“Nothing inside”, Perseverate: “blood, blood, blood”Resistance to food, labile mood
Case Presentation-8: Ms. A
Nov 2-5: Meds:
○ Epival 875 mg/d, Seroquel 350 mg/d, Clonazepam 2 mg/d
“Can’t see”, “Can’t swallow”, more tremor, disorganized
Antipsychotic prn’sLoxapine Seroquel
Nov 2 5 25
Nov 3 17.5 25
Nov 4 10 25
Case Presentation-9: Ms. A Nov 5:
Perseverate: “blood, blood, blood”Thinks food is poisonedPacing, Didn’t sleep
○ CPK= 18,245 (normal < 230)○ WBC= 12,400 (normal < 11,000)○ T= 37.4○ BP = 170/90 (not labile)○ PR = 120
Case Presentation-10 What is your diagnosis?
What is the differential diagnosis?
What is your next step?
Case Presentation-11: Ms. A Nov 5-7:
Nov 5: ○ Transfer to Acute Medicine Step Down: NMS?○ Antipsychotics stopped
Nov 6: “lead pipe rigidity”, DantroleneNov 7: Bromocryptine added, Desat 80% O2
Transfer to ICU after code blue (aspiration LLL)○ EEG: Mild slowing left side○ Troponin 0.53 (normal < 0.10)Temperature CPK WBC
Nov 5 37.4 18,245 12,900
Nov 6 36-38.2 12,210 13,900
Nov 7 37. 2 3354 15,800
Nov 8 38.3 666 8100-14,600
Nov 9 37.3 471 8800
Case Presentation-12: Ms. A Nov 8-12 (ICU):
Nov 8: Midazolam drip, no clonazepam, stop Epival.Nov 9:
○ Repeat EEGMild diffuse encephalopathy, intermittent slowing ( 1-3 Hz delta)
○ CT headNil acute changes
Nov 12:○ Rigidity, voluntary component, Rabbit-like jaw tremor
Case Presentation-13
What is the next step?
Case Presentation-14: Ms. A Nov 12:
BT ECT initiated in ICU (rocuronium used)Hypotension, bolus helped
Nov 13-Dec 6 (ICU then Acute Medicine Unit)BT ECT’s times 9, 50% energy dosingSlow improvement in alertness, rigidity, speechTremor and “rabbit” jaw movements goneSmiling, recognizing familyFeeding tube but eating someTransferred to Provincial Institution from STAT on Dec 10 for
further treatment…
Catatonia: DSM-IV criteria
Motor immobility as evidenced by catalepsy (including waxy flexibility) or stupor;
Excessive motor activity (purposeless, not influenced by external stimuli); Extreme negativism (motiveless resistance to all instructions or
maintenance of a rigid posture against attempts to be moved) or Mutism; Peculiarities of voluntary movement as evidenced by posturing, stereotyped
movements, prominent mannerisms, or prominent grimacing Echolalia or Echopraxia.A. At least 2 of the above features B. Due to mental (eg: Schizophrenia or Mood Disorders) or medical disorderC. Does not occur exclusively during the course of a Delirium
*Gegenhalten, Mitgehen, Automatic Obedience, Ambitendency
Fink Catatonia Scale (1996): www.ukppg.org.uk/catatonia.html
Catatonia: Phenomenology-1 Posturing
Spontaneous maintenance of posture (s), including mundane (e.g. sitting or standing for long periods without reacting).
○ Limb posturing○ “Psychic pillow”○ Staring
Catatonia: Phenomenology-2 Rigidity
Maintenance of a rigid position despite efforts to be moved, exclude if cog-wheeling or tremor present
NegativismApparently motiveless resistance to instructions or
attempts to move/examine patients. Contrary behaviour, does exact opposite of instruction.
Waxy FlexabilityDuring reposturing of patient, patient offers initial
resistance before allowing himself to be repositioned, similar to that of a bending candle.
Catatonia: Phenomenology-3 Gegenhalten
Continuous involuntary sustained muscle contraction When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched.
Mitgehen"Anglepoise lamp" arm raising in response
to light pressure of finger, despite instructions to the contrary.
Catatonia: Phenomenology-4 Ambitendency
Patient appears "motorically stuck" in indecisive, hesitant movement.
Automatic Obedience
Exaggerated cooperation with examiner's request or spontaneous continuation of movement requested.
Lethal Catatonia (Kahlbaum 1874)Mann et al., Amer. J. Psych. 1986; 143:11, p. 1374-81
Classic description (Pre-neuroleptic era):Intense motor excitement followed by hyperthermia and
exhaustion or stuporOften prodromal phase of insomnia, anorexia, labile
moodMay demontrate catatonic signs, and be delirious-like
(disorganized thinking, psychosis, destructive)May have rigidity, or flaccidity, in terminal stagesPresence of acrocyanosis in someFatal in 75-100%
Lethal Catatonia
Post-neuroleptic era:Stupor may be predominant presentationAntipsychotics, benzo’s, etc. can decrease
excitementUp to 10% inpatient psych. admission?Fatal in 60%?
Neuroleptic Malignant Syndrome: DSM-IV criteria
A. Development of severe rigidity and elevated temperature associated with the use of neuroleptic medication
B. 2 of the following: diaphoresis, dysphagia, tremor, incontinence, change LOC, mutism, tachycardia, elevated or labile BP, elevated WBC or CPK (may also observe myoclonus)
C. Not due to another substance, or neurological disorder, or other general medical condition
D. Not better accounted for by a mental disorder
NMS and Medications
Antipsychotic medications Withdrawal of L-Dopa or dopamine
agonists Prochlorperazine (Stemetil) Metoclopramide (Maxeran) Tetrabenanzine (Nitoman)
NMS risk factors
Exhaustion and Dehydration Agitation, Stress, Psychosis Higher potency, rapid titration, multiple I.M.’s Environmental heat a factor? Previous history (trait vulnerability?)
17% hx. of NMS30% will develop NMS again upon re-challenge
NMS: Pathogenic Mechanisms
Figure 1. Simplified Pathophysiology of Neuroleptic Malignant Syndrome (NMS), and Elements of Sympathoadrenal Dysregulation
From: Strawn J. Neuroleptic Malignant Syndrome (review). Am J Psychiatry 164:870-876, June 2007
Item Sachdev NMS Scale (2005): total=36 Subtotal ScoreOral temperature 0 1 2 3 4 5 6 ____ ____
•Rigidity 0 1 2 3 ____
•Dysphagia 0 1 ____
•Resting tremor 0 1 2 ____ ____
•Systolic BP 0 1 ____
Diastolic BP 0 1 ____
•Tachycardia 0 1 ____
•Diaphoresis 0 1 ____
•Incontinence 0 1 ____
•Tachypnea 0 1 ____ ____
Altered LOC 0 1 2 3 4 5 6 ____ ____
•Posturing 0 1 ____
•Poverty of speech 0 1 ____
•Mutism 0 1 2 ____
•Choreiform 0 1 ____ ____
•Dystonia 0 1 ____
•CK level (U/L) 0 1 2 3 4 ____
•Leucocytosis 0 1 2 ____ ____
CK level (U/L): < 200 rate “0”
200–400 rate “1” (0 if i.m. injection in previous 24 h)
400–1000 rate “2” (1 if i.m. injection in previous 24 h)
1000–10,000 rate “3”
> 10,000 rate “4”
Sachdev NMS Rating Scale: CK Levels (Psych Res. 2005)
NMS Course 0.2% of patients 16% develop within 24 hrs of exposure 66% develop within 1 week of exposure Virtually all by 1 month of exposure 63% recover within 1 week of elimination Virtually all recover by 1 month of elimination Should wait 2 weeks at least after recovery before
re-challenge with antipsychotics 10-20% mortality rate Few have persistent catatonic and/or parkinsonian
state (Caroff, S. J. Clin. Psychopharm. 2000)
NMS Treatment: Information
Neuroleptic Malignant Syndrome Information Service (NMSIS):24 hr. Hotline for professionals: 1-888-667-8367www.nmsis.orgInformation: 1-888-776-6747Non-profit clinical and research group—Drs. Caroff,
Mann, Campbell (U. Penn)
NMS: Catatonic and Non-CatatonicLee JW, Aust NZ J. of Psych. 2000; 34(5): 877-8
Antecedent Catatonia may predispose to catatonic NMS
Non-catatonic NMS more likely preceded by severe EPS and delirium
NMS and Catatonia: Similarities Appearance of catatonic symptoms in NMS Appearance of rigidity and hyperthermia in (lethal)
catatonia Treatment with Lorazepam in NMS (Francis A. CNS
Spectrum 2000) and Catatonia can improve ECT effective in both N=292 Lethal Catatonia patients from 1960 (Mann S.
Am J Psychiatry 1986; 143:1374-1381)Unable to distinguish from NMS in 22%
NMS and Catatonia: Differences Extreme (lead pipe) rigidity uncommon in
catatonia Stereotypic signs of catatonia unusual in NMS Excitement then hyperthermia pre-neuroleptic in
lethal catatonia; rigidity then hyperthermia post-neuroleptic in NMS
Potentially effective treatments for NMS (dopamine agonists, dantrolene) less proven in catatonia
Similar Conditions: DDx Malignant Hyperthermia Anticholinergic Delirium Heatstroke Manic Delirium Serotonin Syndrome Abusable alcohol or drug withdrawal (eg: delirium
tremens) and intoxication (eg: Ecstasy) Status epilepticus and other CNS conditions Systemic Conditions: infection, hyperthyroidism,
pheochromocytoma, adrenal cortical abnormalities, other causes of rhabdomyolysis (eg: collapse)
Catatonia In the modern era, the most likely
psychiatric cause for catatonia is Bipolar Disorder, esp. Mania
More likely when severe mania
Kahlbaum, Bleuler, Kraepelin all noted mood disturbance preceding catatonia
From: Taylor MA, Am J Psych 2003
Prevalence of Catatonia and Mania
From: Taylor MA, Am J. Psych 2003
Pathogenic Mechanisms: Catatonia
Neurochemical substrates:D2 antagonists can worsen catatoniaGABA-B, 5-HT1A agonists promote catatoniaGABA-A, 5-HT2A, NMDA agonists reduce catatonia
G. Northoff (2000):www.bbsonline.org/documents/a/00/00/22/44/
bbs00002244-00/bbs.northoff.htm54 page paper“Top Down Modulation”: subcortical and cortical circuits
reciprocally connectMore GABA-mediated, rather than D2 mediated
From: Northoff 2000
Modulation in Catatonia
From: Northoff 2000
The Frontal Lobes and its Connections
From: Northoff 2000
Catatonia and PD: Differences
GABA (lorazepam)
- Gaba-ergic mediated neuronal inhibition in medial orbitofrontal cortex - Modulation of functional and behavioral inhibition
NMDA (Amantadine)
- Down-regulation of glutamatergic-mediated overexcitation in prefrontal and orbitofrontal-parietal pathways
- Down-regulation of glutamatergic-mediated overexcitation in subcortical pathways
Dopamine - Top-down modulation of striatal D-2 receptors predisposing for neuroleptic-induced catatonia
-Compensation for striatal D-2 receptor deficit with "normalization" of "bottom-up modulation
Catatonia Parkinson
Catatonia Treatment: Review of Lit.Hawkins et al., Int. J. Psych. Med. 1995; 25(4): 345-69
N=178, 1985-1994 published cases Benzo’s effective in 70% (Lorazepam) ECT effective in 85% Antipsychotics effective in 7.5%, or may
even worsen symptoms (neuroleptic-induced catatonia)
Catatonia: Treatment Rule out medical condition Lorazepam 1-12mg/day, up to 72hrs. Trial
Specific GABA-A agonist Dantrolene to be considered if rigidity ECT is treatment of choice May consider mECT if recurrent Others:
Atypical Antipsychotic? (not for lethal catatonia)Amantadine?Memantine?
NMS Treatment: Biological
Discontinue Antipsychotic Drug Supportive Medical Treatments Mild to Moderate NMS:
Bromocryptine 2.5-5 mg q8h (up to 30mg/d)Amantadine 100mg q8h (to 200-400mg/d)May use Benzo (eg: Lorazepam 1-8 mg/d)
Moderate to Severe NMS:Dantrolene IV 1-2.5mg/kg (1mg/kg q6h)ECT (bilateral, may even be daily)
NMS and ECT: Review of Lit.Trollor and Sachdev, Aust.NZ J. of Psych 1999; 33:650-59
45 published cases from 1966, and 9 new cases Catatonia manifested in 76% of cases 63% complete and 28% partial recovery with ECT Onset of ECT response average 4 treatments,
generally by 6 treatments 4 cases of cardiovascular complications Supports the use of succinylcholine unless familial
malignant hyperthermia—only one case of hyperkalemia following ECT for NMS
NMS and ECT: Potential Use
Trollor and Sachdev:Severe NMSDifferental between NMS and catatonia uncertainPsychotic depression is the underlying disorderCatatonia predominates in NMS
Catatonia Treatment AlgorithmFilip Van Den Eede et al. European Psychiatry 2005
Conclusions It can be difficult to differentiate NMS and catatonia in
practice, and definitive treatments are similar
Use of antipsychotics with less dopamine blockade is probably less likely to produce NMS and less likely to be severe, according to the dopaminergic hypothesis
Both NMS and catatonia can be safely and effectively treated with ECT, providing precautions are considered