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03/12/2012

Psychosis Clinical Academic Group (CAG) RAPID TRANQUILLISATION

LEARNING FROM END-STAGE RAPID TRANQUILLISATION IN WOMEN’S PICU

DR FAISIL SETHI CONSULTANT PSYCHIATRIST EILEEN SKELLERN 1 PSYCHIATRIC & PICU LEAD CONSULTANT (PSYCHOSIS CLINICAL ACADEMIC GROUP)

MAUDSLEY HOSPITAL SOUTH LONDON AND MAUDSLEY NHS FOUNDATION TRUST

VICE CHAIR NATIONAL ASSOCIATION OF PSYCHIATRIC INTENSIVE CARE AND LOW SECURE UNITS (NAPICU)

Intramuscular Medication - • • 0.5-2mg IM every 1-2 hours until symptoms controlled • Cmax: PO 1-6hrs; IM 45-75min; IV 5-10min • Onset of efficacy: 5-30min • Elim half-life: 8-24hrs • Metabolites: not active • No accumulation with repeated doses (unlike )

Intramuscular Medication - Intramuscular Medication - Benzodiazepines • (unlicensed) • • Cmax: 1 min • Effective in 5-20min • 10mg at least as effective as 7.5mg • Elim half-life: 1-4hrs(p); 1-20hrs(m) • Peak in a few minutes • Metabolites: active • Peak plasma 5x higher than oral dosing • Diazepam • Onset of efficacy in 30min • Cmax: 1-2hrs • Max combined dose 20mg/day • Not much faster than oral in terms of efficacy • Max IMs in 24hrs is three • Elim half-life: 15-80hrs(p); 30-200hrs(m) • Metabolites: active • Short-term only: max for 3 consecutive days • IM erratically absorbed • No simultaneous benzos (2hrs apart) • Accumulation in chronic dosing

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Intramuscular Medication - Intramuscular Medication - Antipsychotics Antipsychotics • Haloperidol • • Usually 30-60min till achieved • Onset of efficacy 30-60min • Max 18mg per day (IM) • Usual dose 5.25-9.75mg. • Current concerns: • IMs at least 2hrs apart. • Reilly et al (Lancet 2000) • Max doses in 24hrs is three. • QTc Prolongation • Max combined dose in 24hrs is 30mg. • Torsades de pointes • SPC: Cardiac Ax & ECG • Benzos can be given at the same time. • • Specific anti-agitation effect vs non-specific effect.

RT Medication -Other

• (PO/IM) • IM Combinations: + • IM Combinations: Haloperidol + Promethazine • IM X • IM Amylobarbitone Sodium 500mg X • IM X • IM Acetate (?) • IV Medn: Diazepam (?Haloperidol) (?Midazolam)

Zuclopenthixol acetate single dose Acuphase 45 40

• Cmax: On average 24-36 hours post-IM 35

• Sedation begins in 2hrs, but peaks after 12hrs 30 • Effects can last up to 24hrs 25 • 50-150mg; max 400mg in a 2-week period (and 20 max 4 injections in that time) Extrapolated • Injections at least24hrs apart 15 • This is clearly not RT!!! 10

• BNF states you can go to LAI with last injection of 5 Acuphase! 0

0 12 24 36 48 60 72

Hours

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ECT –Do We Use It Enough? Anti-Aggressives

• RCPsych Consensus Group (2003): Major • Lithium (PO) Depression; Mania; Acute Schizophrenia; Catatonia. • (LAI) / / / • NICE (2005): Severe Depressive Illness; Catatonia; Zuclopenthixol (SAI and LAI) Prolonged or Severe Manic Episode (not in the mx of schizophrenia!) • Benzodiazepines (for short-term) (IM) • RCPsych ECT Handbook (2004): Severe mania that has not responded to treatment of choice; • (loading –PO) Catatonia when Lorazepam has been ineffective

Hyperthermia Syndromes In Psychiatry Ahuja N & Cole A. Advances In Psychiatric Treatment (2009) RT/ Sedation/ Anaesthesia

DIFFERENTIALDIAGNOSES • RT (Urgent Sedation): reduction in agitation and Neuroleptic Malignant Syndrome aggression via light sedation, allowing a thorough Syndrome psychiatric assessment Malignant (Lethal) Catatonia AnticholinergicToxicity Syndrome • Deep Sedation: reduction of consciousness and Exertional Heat Stroke motor and sensory activity, verbal contact is Sepsis progressively lost Encephalitis, Meningitis Thyrotoxicosis Overdose of Sympathomimetics and Other • Anaesthesia: unconsciousness, analgesia and or Withdrawal muscle relaxation. Loss or airway control and protective reflexes.

Psychiatric Medications and Nasogastric Tubes Sedative Agents In The ICU

• Drug Classes: • : ; Remifentanil; Sulphate • Benzos: Diazepam; Lorazepam; Midazolam • Other: ; ; ; • Aims of sedation/analgesia: facilitate intubation/ventilation; provide relief from /pain; decrease O2 requirements

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Zuclopenthixol decanoate 1/52 LAIs

Flupenthixol Decanoate Oil Decanoate Oil Haldol Decanoate Oil Pipothiazine Decanoate Oil Zuclopenthixol Decanoate Oil Risperdal Consta BiodegradableMicrospheres Palmitate Crystalline Olanzapine Pamoate Crystalline

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Weeks

Haloperidol decanoate 2/52 Olanzapine pamoate 405mg every 4/52

60

50

40

30 P la sm a le v el ng / ml

20

10

0 2 4 6 8 10 12 14 16 18 20 22 24

Weeks 0 10 7 13 2 19 25 4 31 3 7 6 43 49 855 61 1067 7 3 7912 85 91 14 9 7 10 31610 9 11 5 1812 112713203 13 9 14 225 15 1 15 24716 3 16 92617 5 18 1 2818 7 193

LAIs

• Dose Response Relationships Are Complex • Most LAIs reach steady-state after 4-5 half- lives (over 2 months!) • But prior to steady-state, plasma profile can vary several-fold • Loading (initiation) strategies allow for earlier steady-state • Is Loading/Initiation a bridge between the acute and maintenance role of the LAI?

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LAIs –Loading? Valproate Loading (pre-emptive)

Name Delivery LoadingStrategy • Antimania at levels of 45-125 µg/ml Flupenthixol Decanoate Oil ↑ frequency Fluphenazine Decanoate Oil • > 110 µg/ml: S/E > treatment benefit • e.g. HDwkly will quadruple plasma Haldol Decanoate Oil levels in the short-term • Pipothiazine Decanoate Oil • Expect EPSEs and other S/Es Antimanic response as early as day 5 • min effective dose not clear! Zuclopenthixol Oil • Keck et al 1993: 20mg/kg Decanoate Risperdal Consta Biodegradable Not possible due tolow release prior • Hirschfield et al 1999: 30mg/kg (D1+2); Microspheres to approx 24 days 20mg/kg (D3-10) Paliperidone Palmitate Crystalline Initiation strategies have been • ?60 kg lady. Load with 1500mg (750BD), and Olanzapine Pamoate Crystalline developed to increase immediate plasmalevels, but SS still takes check level in 3-5 days. months

In Summary

• PICU patients are all challenging • Some more than others • End-stage Rapid Tranquillisation scenarios are some of the most challenging in the PICU • These cases also lead to good learning opportunities • Innovative practice in the face of serious challenge is a core attribute of a PICU team

My Learning: Psychosis Clinical Academic Group (CAG) • and dose-response • IM, IV and ECT Tx in ES-RT • Knowledge of psychiatric and medical syndromes • Keep out-of-date and up-to-date • Look for patient-specific factors THANK YOU • High quality medical liaison • Consider the treatment setting early • Treatment is multidisciplinary; receive and share learning with the team

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