The summaries below are meant for a psychiatry resident level of training and above (i.e. inappropriate/excessive level of detail for medical student purposes). Please note this page is incomplete. The information below should not replace clinical judgement. Abbreviations are used and levels of evidence are omitted for brevity purposes

• Late onset schizophrenia = onset 40-60/65 yo
  Very-late onset SCZ-like psychosis = onset > 65 vs 60 yo
  Late onset bipolar disorder = onset > 50 yo
  Late-life depression = onset > 60 yo
  Late onset Alzheimer’s = onset > 60 yo
• Metabolic syndrome = 3+/5 following: Waist circumference > 102 cm (40″) in men OR 88 cm (35″) in women; BP > 130/85 mmHg; Triglyceride > 1.7 mmol/L (150 mg/dL); HDL < 1 mmol/L (40 mg/dL) in men OR 1.3 mmol/L (50 mg/dL) in women; Fasting glucose > 5.6 mmol/L (100 mg/dL) or abnormal A1C (5.7 to 6.4 percent)

• Additional f/u investigations for clozapine: CBC q wk x 1st 6 mo (12 mo if rechallenging clozapine after moderate leukopenia) –> q 2 wk x next 6 mo –> q 4 wks; vitals 6-8 hrs post-dose for 1st 4 doses of initiation; vitals + S&S myocarditis (fever, fatigue/malaise, chest pain) q2d (if inpt) vs q wk (if outpt) x 1st mo; CRP + troponin q wk x 1st 4 wks, at wk 6, at wk 18, at 6 mo then q 6 mo; ECG at 6 mo then q yr; echo at 6 mo and PRN; baseline nor/clozapine serum level

Mood Disorders

• Baseline investigations for bipolar disorder: History, collateral, physical exam, rating scales (Young Mania Rating Scale, Mood Disorders Questionnaire, mood chart), UDS, CBC, chem panel, calcium, albumin, U/A, +/- 24 hr CrCl (if renal disease), liver panel, TSH, lipid panel, fasting glucose, BMI, +/- ECG (if 40+ / PRN), +/- beta-hCG, +/- PRL, +/- HLA-B*1502 genotyping in Hans Chinese
• F/u investigations for lithium: Li, CBC, chem panel, U/A, calcium, albumin, TSH +/- T3, vitals, BMI, fasting glucose, lipid at 6 month mark (vs q 3 mo x 1 year) then annually (vs q6mo)
• F/u investigations for VPA: CBC, full liver panel, menstrual hx (for PCOS) q 3-6 mo x 1st yr –> q yr; VPA serum levels at therapeutic dose x 2 –> q 3-6 mo

Neurocognitive Disorders

• Baseline investigations for cognitive impairment: History, collateral, physical exam, cognitive testing, functional testing, depression screening, +/- neuropsych testing, +/- UDS, +/- heavy metal, CBC, chem panel, calcium, albumin, +/- PO4, +/- Mg, +/- NH3, U/A, liver function tests, TSH, vitamin B12, +/- folate, fasting glucose or A1C, lipid panel, BP, ESR, +/- HIV, +/- neuroimaging, +/- CSF, +/- genetic testing/counselling

Eating Disorders

• Investigations for eating disorders: History, collateral, rating scales, physical exam (orthostatic vitals, hydration status, height/weight +/- growth chart, sit up-squat-stand test), CBC, ferritin, transferrin, B12, zinc, chem panel, ext lytes, U/A, full liver panel, TSH, T3, T4, lipid panel for AN, ECG, +/- stool exam if GI bleeding/abdo c/o/anemia, amylase if purging. If underweight > 6 mo = abdo u/s, FSH, LH, estradiol or testosterone, DEXA scan.

Major depressive disorder

• Early improvement = 20-30% improvement at 2-4 wk mark; Expected onset of full response to ADT for MDD = 6-12 wks
• 1st line meds = all SSRIs, all SNRIs excl levomilnacipran, vortioxetine, bupropion, mirtazapine
  • ADT w/ superior efficacy per CANMAT = sertraline, escitalopram, mirtazapine, venlafaxine > citalopram (L2E)
  • Best overall tolerability and efficacy = escitalopram, vortioxetine

• 2nd line meds = levomilnacipran, vilazodone, trazodone, quetiapine, TCAs, moclobemide, selegiline

• Psychological tx for MDD
  • For maintenance tx: 1st line = CBT, mindfulness-based cognitive therapy; 2nd line = IPT, behavioral activation, cognitive-behavioral analysis system of psychotherapy; 3rd line = long-term psychodynamic; 2nd line adjunct = bibliotherapy, peer interventions (eg self-help groups)

Bipolar disorder

• Takes ~2 weeks for onset of action w/ 1st line agents for BID MDE vs 1-3 weeks for onset of action with Li
• Antidepressant monotherapy not recommended if prior antidepressant-induced hypo/mania, rapid cycling, or mixed features
  • Risk factors for manic switch: BID, prior hypo/manic switch, SNRIs and TCAs > SSRI and bupropion
• Rapid cycling
  • Discontinuing offending perpetuating factors, most commonly antidepressants (including adjuncts; will require taper, not abrupt discontinuation), psychostimulants, substance use, and hypothyroidism
  • There is insufficient evidence to support a particular 1st line agent. Instead, consider medication efficacy in the standard treatment of acute episodes / maintenance treatment. Combination therapy is often required. Lithium, divalproex, olanzapine, and quetiapine have all been equally efficacious for maintenance treatment. Lamotrigine is not effective for maintenance treatment
• Tx of comorbid primary anxiety and related disorder
  • 1st line = quetiapine, gabapentin
  • 2nd line = serotonergic ADT, olanz-fluox combo, olanz, DVP, lamotrigine
  • 3rd line = pregabalin, risperidone, aripiprazole, lithium, medium/long-acting benzo
• Tx of comorbid ADHD (BD should be stable x 3 mo w/ good community supports to monitor before starting psychostimulants. Start low / go slow, closely monitor)
  • 1st line = bupropion (in BIID)
  • 2nd line = methylphenidate, mixed amphetamine salts, modafanil, CBT
  • 3rd line = Vyvanse, atomoxetine, venlafaxine, nortriptyline, desipramine

GAD

• 1st line = paroxetine, escitalopram, sertraline, venlafaxine, duloxetine, pregabalin
• 2nd line = diazepam, lorazepam, alprazolam, bromazepam, buspirone, quetiapine XR, hydroxyzine, imipramine, vortioxetine, bupropion XL
• 2nd line adjunct = pregabalin
• 3rd line adjuncts = quetiapine, risperidone, olanzapine, aripiprazole

Social anxiety disorder

• 1st line = paroxetine, escitalopram, sertraline, fluvoxamine, venlafaxine, pregabalin
• 2nd line = gabapentin, clonazepam, alprazolam, bromazepam, phenelzine
• 3rd line adjuncts = risperidone, aripiprazole, paroxetine, busprione

Agoraphobia / panic disorder

• 1st line = fluoxetine, fluvoxamine, paroxetine, es/citalopram, sertraline, venlafaxine
• 2nd line = mirtazapine, clomipramine, imipramine, clonazepam, diazepam, lorazepam, alprazolam
• 2nd line adjuncts = clonazepam, alprazolam
• 3rd line adjuncts = aripiprazole, olanzapine, risperidone, divalproex, pindolol
• 3rd line = duloxetine, bupropion, moclobemide, phenelzine, tranylcypromine, olanzapine, quetiapine, risperidone, DVP, gabapentin, levetiracetam

PTSD

• No role for benzodiazepines

OCD

• 1st line med = all SSRIs except citalopram
• 1st line psychotherapy = CBT including ERP
• 2nd line med = clomipramine > citalopram, mirtazapine, venlafaxine XR
• 1st line adjuncts = risperidone, aripiprazole
• 2nd line adjuncts = quetiapine, memantine, topiramate

ADHD

• 1st line = long-acting psychostimulant
• 2nd line = switch to other class of long-acting psychostimulant
• 3rd line = intermediate/short-acting psychostimulant, atomoxetine, guanfacine XR (not recommended for adult ADHD)
• 4th line = clonidine, bupropion, impramine, atypical antipsychotic for comorbidities (has evidence for hyperactivity in ASD+ADHD), modafanil (no efficacy for adult ADHD)

Subclinical Hypothyroidism

• General consensus to treat w/ L-thyroxine if TSH > 10
• Tx when TSH betw UNL (4-5 in adults; different in geri and pregnancy) and < 10 is controversial
  • If TSH 7-9.9 = tx all (only if sx if geri)
  • If TSH betw UNL to < 7 = tx < 65 yo only if symptomatic or women trying to conceive (don’t tx > 65 yo)
• Monitor for progression to overt hypoTSH (eg q 3 mo)

Antipsychotic-Induced Hyperprolactinemia

• Repeat fasting PRL if initial PRL 21-40 ng/mL
• Asymptomatic = no tx
• Symptomatic = reduce dose or switch to less offensive AP (aripiprazole, quetiapine, CLZ); aripiprazole adjunct; adjunctive estradiol and progestin to tx estradiol deficiency in women vs adjunctive testosterone to tx testosterone deficiency in men (does not tx the hyperPRL); adjunctive dopamine agonist (eg bromocriptine)

Antipsychotics

• Do not rechallenge clozapine (all else can potentially rechallenge given appropriate surveillance/management/prophylaxis) if = myocarditis, cardiomyopathy, QTc > 500, ANC < 500/uL (unless maybe there was confounding factors)

	Relative efficacy for positive psychotic symptoms	EPS	HyperPRL	Metabolic	Sedation	QTc	Breastfeeding Risk	Special Admin
Haloperidol	Med	High		Low	Low	High (esp IV)	Best TAP
Chlorpromazine	Higher	Med		Med-High	High	High
Risperidone	*Higher*	Med		Med-High	Low
Paliperidone	Higher	Med		Med-High		Low
Lurasidone	Lower	High		Low		*Low*		Take w/ food
Ziprasidone	Med	Med		*Low*	Low	High		Take w/ food, BID
Olanzapine	Higher	Low		*High*	Med		Best AAP (1st choice)
Quetiapine	Med	Low	Low	*High*	Med	High
Asenapine	Med	Low		Low		Low		SL, poor taste (not good if paranoid), BID (OD if overly sedating)
Clozapine	*Higher* (gold standard for TRS)	Low	Low	*High*	High			Multi SE, bloodwork
Aripiprazole	Lower	Med (akathisia)	Low	*Low*	Low	*Low*
Brexpiprazole	Lower	Low		Low
Cariprazine	Lower			Low

Antidepressants

	Evidence for MDD	Evidence for Anxiety and Related D/o	Other Indications	GI Upset	Weight Gain	Sexual Dysfunction	QTc	Peripartum
Escitalopram (Cipralex)	*1st line w/ superior efficacy				*Lowest	Medium	High
Citalopram (Celexa)	1st line					*Highest	High	Last choice SSRI in breastfeeding
Sertraline (Zoloft)	*1st line w/ superior efficacy	1st line PTSD				*Highest	Best if AT RISK	1st choice SSRI in breastfeeding
Fluoxetine (Prozac)	1st line	1st line PTSD				*Highest	High	Last choice SSRI in breastfeeding
Paroxetine (Paxil)	1st line	1st line PTSD			High	*Highest	High
Fluvoxamine (Luvox)	1st line	2nd line PTSD				*Highest	High
Venlafaxine (Effexor)	*1st line w/ superior efficacy	1st line PTSD	Neuropathic pain			*Highest	High
Desvenlafaxine (Pristiq)	1st line		Neuropathic pain			Low
Duloxetine (Cymbalta)	1st line		Neuropathic pain			*Highest	Best if already prolonged
Levomilnacipran (Fetzima)			Neuropathic pain		*Lowest	Medium
Bupropion (Wellbutrin, Zyban)	1st line		3rd line agent for ADHD		*Lowest	*Lowest	Best if already prolonged
Mirtazapine (Remeron)	*1st line w/ superior efficacy	2nd line PTSD	– Akathisia – Sleep (lower doses)	*Lowest	*Highest	*Lowest
Vortioxetine (Trintellix, Brintellix)	*1st line w/ superior efficacy				*Lowest	High	Best if already prolonged
Vilazodone (Viibryd)					*Lowest	*Lowest
Most TCAs			– Neuropathic pain – Sleep – Imipramine 3rd line agent for ADHD		High (most TCAs)		High (most TCAs)	Ideally avoid doxepin in breastfeeding
Moclobemide						*Lowest
Phenelzine		2nd line PTSD
Trazodone			Sleep

Benzodiazepines

• Longest half-life = flurazepam > diazepam
• Shortest half-life = midazolam > alprazolam
• Safest in liver dysfunction = “LOT” (lorazepam, oxazepam, temazepam); other benzos are contraindicated

Substance Use Adjuncts

• Contraindications for naltrexone = severe liver disease (Child-Pugh Score C, ALT and AST > 3x UNL), recent opioid use (within 5 days for short-acting vs 7 days for long-acting); caution with mild hepatic dysfunction and mod-severe kidney dysfunction
• Contraindications for acamprosate = severe renal dysfunction (ie GFR < 30; caution if mild-mod), adherence issues; caution if pregnancy, breastfeeding or < 60 kg
• If prolonged QTc = naltrexone, gabapentin not classified. No info re disulfiram or acamprosate.

Atypical Antipsychotics for psychotic/bipolar disorders

• Average time to reach steady state for most LAI = 8-12 weeks
• Aripiprazole (lowest dose ever seen is 150 mg (not effective) vs 200 mg; lowest frequency ever seen is q14d; 350 mg is possible w/ 400 mg syringe)

Aripiprazole PO	Abilify Maintena q4wks +/- 1 week
10 mg	300 mg
15 mg	400 mg
20+ mg	600 mg (not practically used)

• Risperidone / paliperidone
  • Risperidone PO for psychosis/mania = start at 1 (to 3) mg/day in 1-2 divided doses –> increase by 1-2 mg/day as fast as q 24 hr (but try to assess for full effect for > 1 wk vs few weeks) –> target dose 2-8 mg (max 8 mg (clinically recommended max dose) vs 16 mg (per manufacturer’s labelling))
  • Invega Sustenna (lowest frequency ever seen is q 2 weeks)
  • Invega Trinza (lowest frequency ever seen is q 8 weeks, equivalent to Sustenna q 3 weeks)
    • Prerequisite = stable on Sustenna x 4 mo + last 2 doses consistent

Risperidone PO	Risperidone Consta q2wks	Paliperidone PO	Invega Sustenna q4wks +/- 1 wk	Invega Trinza q12wks +/- 2 wks
1 mg	12.5 mg	< 3 mg	–	–
2 mg	25 mg	3 mg	50 mg	175 mg
3 mg	(25 to) 37.5 mg	6 mg	75 mg	263 mg
4 mg	(37.5 to) 50 mg	9 mg	100 mg	350 mg
5 mg	37.5-50 mg	–	–	–
6 mg	50 mg	12 mg	150 mg	525 mg

• Quetiapine
  • For psychosis = start at 100 mg –> increase by 100 mg daily to target 600 mg (max 800 mg)
• Lurasidone
  • For BID MDE = start at 20 mg PO OD in evening w/ 350+ calories (can take initially w/out food for ease of side effects) –> increase by 20 mg q 2+ days to target 20-60 mg (max 120 mg/d)
• Clozapine
  • Minimum for clozapine-refractory SCZ = 1100 nM/L (350 ng/mL)
    Maximum = 2100 nM/L (700 ng/mL)
    Seizure-inducing = 3600 nM/L (1200 ng/dL)
  • nM/L = Canadian measurement
    ug/L (microgram/L) = ng/mL (Cortisol conversion to nmol/L, µg/L, µg/dL, µg/100mL, µg%, ng/mL . Online converter from conventional units to SI units | UNITSLAB.COM)

Mood Stabilizers

• Lamotrigine = typical max 200 mg/d (some literature for max 400 mg/d)

Antidepressants and Adjunctive Antipsychotics for Depression/Anxiety

Med	Starting Dose	Smallest Formulation in Canada	Titrate Schedule	Target Dose (per 2023 CANMAT MDD guidelines)	Max Dose
Escitalopram (aka Cipralex)	10 mg PO OD for MDD vs 5-10 mg PO OD for GAD	10 mg tablet	5-10 mg/d q 1+ wk	10-20 mg PO OD for MDD	Usually 20 mg PO OD for MDD vs 40 mg PO OD for OCD
Citalopram (aka Celexa)	10 mg PO OD for GAD vs 20 mg PO OD for MDD		10 mg/d q week (q 3-4 d if inpt)		40 mg PO OD (20 mg/day if > 60 yo)
Sertraline (aka Zoloft)	50 mg PO OD for MDD	25 mg capsule	25-50 mg PO OD q 1 week for MDD (q3d w/ antipsychotic if psychotic features)	50-200 mg PO OD for MDD	300 mg PO OD
Fluvoxamine (aka Luvox)	50 mg PO OD for MDD	50 mg tablet		100-300 mg/d in BID dosing for MDD	300 mg/d in BID dosing
Paroxetine (aka Paxil) IR	10-20 mg PO OD for anxiety vs 20 mg PO OD for MDD	10 mg IR tablet	10 mg/d q 1 week for anxiety vs 10-20 mg/d q 1 week for MDD	20-50 mg PO IR OD for MDD	50 mg PO OD for MDD vs 60 mg PO OD for anxiety
Paroxetine (aka Paxil) CR	12.5-25 mg PO OD for anxiety vs 25 mg PO OD for MDD	12.5 mg CR tablet	12.5 mg/d q 1+ week		62.5 mg PO OD for MDD vs 75 mg PO OD for anxety
Vortioxetine (aka Trintellix)	5-10 mg PO OD	5 mg tablet	5-10 mg/d q 1 wk	10-20 mg PO OD for MDD	20 mg PO OD
Vilazodone (aka Viibryd)	10 mg PO OD	10 mg tablet	Increase to 20 mg PO OD after 7 days then increase to 40 mg after 7+ days if needed	20-40 mg PO OD	40 mg PO OD
Desvenlafaxine ER (aka Pristiq)	50 mg PO OD for MDD	50 mg ER tablet	Increase to 100 mg PO OD after 6 weeks if no response	50-100 mg PO OD for MDD	100 mg PO OD
Duloxetine (aka Cymbalta)	30 or 60 mg PO OD for MDD/GAD/pain	30 mg DR capsule	30 mg PO OD x 1 wk then 60 mg PO OD x 4-6 wks then 90 mg x 3+ wks then 120 mg PO OD (vs q 3-4d if inpt)	60-120 mg PO OD for MDD/GAD/pain (usually sufficient at 60 mg PO OD)	120 mg PO OD
Levomilnacipran ER (aka Fetzima)	20 mg PO OD for MDD	20 mg ER capsule	Increase to 40 mg PO OD on day 3 then by 40 mg PO OD q 2+ days	40-120 mg PO OD for MDD	120 mg PO OD
Mirtazapine (aka Remeron)	15 mg PO qhs for MDD	15 mg tablet	15 mg/d q 1+ week for MDD	30-60 mg qhs for MDD	60 mg PO qhs
Bupropion (aka Wellbutrin, Zyban)		150 mg 24 hr XL tablet 100 mg 12 hr SR tablet		150-450 mg PO OD as primary agent or adjunct for MDD (daily doses above 300 mg should be given in divded doses)	450 mg PO OD
Amitriptyline (aka Elavil)	25-50 mg PO QHS (or in divided doses; 50-100 mg/d if inpt) for MDD		25-50 mg/d q 1 wk (or q few days if inpt) for MDD	75-300 mg/d for MDD
Clomipramine (aka Anafranil)	25 mg PO OD for OCD	10 mg tablet	Increase to ~100 mg/d in divided doses over the first 2 weeks then increase after 2-3 week PRN for OCD vs 50 mg PO OD q2-3d for MDD	150-300 mg/d in divided doses for MDD	300 mg/d in divided doses
Doxepin	25-50 mg PO qhs	3 mg tablet 10 mg capsule	25-50 mg/d q 3+ days	75-300 mg PO QHS for MDD
Aripiprazole (aka Abilify) adjunct for depression/anxiety	2-5 mg PO OD for MDD	2 mg tablet	5 mg/d q 1-2 weeks	2-10 mg PO OD for MDD	15-20 mg/d for MDD vs 30 mg/d for psychosis
Brexpiprazole (aka Rexulti) adjunct for MDD	0.5-1 mg PO OD	0.25 mg tablet	As fast as 1 mg/d q week	0.5-2 mg PO OD for MDD	3 mg PO OD for MDD vs 4 mg PO OD for SCZ
Cariprazine (aka Vraylar) adjunct for MDD	1.5 mg PO OD for MDD	1.5 mg capsule	Increase to 3 mg PO OD on day 15	1.5-3 mg PO OD for MDD	4.5 mg PO OD for MDD
Quetiapine (aka Seroquel)	50 mg PO QHS for MDD			150-300 mg PO qhs as primary agent or XR as adjunct for MDD

Benzodiazepines

• Lorazepam 1 mg = diazepam 5 mg = clonazepam 0.25 (to 0.5) mg = alprazolam 0.5 (to 1) mg

Cognitive Enhancers

• Donepezil = start at 5 mg PO qAM –> increase in 4 weeks to target dose of 5-10 mg PO OD
• Memantine = start at 5 mg PO OD –> increase by 5 mg/day q week (ie week 2 = 5 mg BID; week 3 = 10 mg qAM + 5 mg qhs) to max 10 mg BID

SUD Adjuncts

• Naltrexone
  • For AUD = +/- start at 25 mg PO OD x several days –> target 50 mg PO OD to max 100 mg PO OD after 1 week
• Gabapentin (for AUD) = start at 300 mg PO OD –> increase by 300 mg q1-2d to effect or target dose 600 mg TID

Other

• Benztropine
  • For PRN acute treatment of EPS = 0.5-*2* PO/IM/IV TID PRN EPS, max 8 mg/24 hrs all sources, can repeat initial dosing (ie max 4 mg single dose) if no improvement in 20-30 min
  • Scheduled = start at 1 mg OD (0.5 mg for Parkinsonism; range from 0.5-4 mg OD or BID) –> increase by 0.5-1 mg q 5 days to target dose 2-8 mg/day in 1-3 divided doses (0.5-6 mg/day for Parkinsonism) –> attempt taper after 7-14 days to several months to see if EPS transient/resolved (otherwise intermittently trial discontinuation)
• Metformin = start at metformin ER/IR 500 mg OD (or metformin IR 250 BID or 500 mg BID) –> increase by 500 mg/d q 2-6 week for ER vs q 7 day (5-30 days) for IR –> target 1000-2000 mg OD for ER vs 750-2000 mg/day in 2-3 divided doses for IR (ER version not covered by AB Blue Cross)
• L-thyroxine = start at 0.025 mg/d –> recheck thyroid function tests after 6 wk –> titrate by 0.025 mg q 3-6 wk until TSH normalizes

• As a general rule of thumb, start at the lowest recommended starting dose
• Can use Cockcroft-Gault equation to calculate CrCl more specifically than default lab eGFR

Atypical Antipsychotics

• No adjustments needed = haloperidol (but use w/ caution in dialysis), loxapine, olanzapine, quetiapine, aripiprazole
• Paliperidone = All forms contraindicated if CrCl < 10 mL/min or on any type of dialysis. All LAI forms contraindicated if CrCl 10 to <50 mL/min but can use modified PO dose (start at 1.5 mg PO OD to max 3 mg PO OD). If CrCl 50 to <80 mL/min, dose adjustment required for PO (start at 3 mg PO OD to max 6 mg PO OD), 1 mo LAI (loading dose 100 mg + 75 mg IM on day 1+7 in deltoid, then 50 mg IM q mo in gluteal/deltoid to max 100 mg IM q mo), and 3 mo LAI (limited data). No dosage adjustment required if CrCl > 80 mL/min (but 6 mo LAI contraindicated if CrCl < 90 mL/min).
• Risperidone
• Lurasidone

Mood Stabilizers

• Lithium
• Valproate = No dosage adjustment required if CrCl > 10 mL/min.
• Gabapentin
• Pregabalin
• Topiramate

Antidepressants

• No adjustments needed = citalopram, fluoxetine, fluvoxamine, (paroxetine)
• Escitalopram = start at 10 mg/d if eGFR < 30 or on dialysis
• Sertraline = start at 50 mg/d if eGFR 15-30 vs start at 25 mg/d if eGFR < 15 or on dialysis
• Venlafaxine = target dose 37.5-112.5 mg/d if eGFR < 30 or on dialysis
• Desvenlafaxine = start at 50 mg q2d if eGFR 30-60 vs max 50 mg q2d if eGFR < 30 or on dialysis
• Duloxetine = start at 30 mg/d if eGFR < 30 or on dialysis
• Bupropion = max 150 mg/d if eGFR < 60 or on dialysis
• Mirtazapine = target 15 mg/d if eGFR < 30 or on dialysis

Benzodiazepines

• Benzos w/ inactive metabolites (ie LOT) preferred
• No adjustments needed = most benzos (including lorazepam and clonazepam) but use w/ caution (monitor for propylene glycol toxicity via osmol gap if using repeated/prolonged/high doses of parenteral lorazepam)
• Chlordiazepoxide = 50% target dose in severe renal insufficiency

Cognitive Enhancers

• No adjustments needed = donepezil, rivastigmine
• Galantamine = caution in moderate renal insufficiency; contraindicated in severe renal insufficiency
• Memantine = target dose 5 mg BID if eGFR 15-30; contraindicated if eGFR < 15

• Definition prolonged QTc (no consensus on definition)
  • Most conservative (per American College of Cardiology) = > 460 (prepubertal), > 470 (postpubertal men), > 480 (postpubertal women)
  • Per SCZ guidelines and many psychiatric papers= > 450 (men), > 460 (women)
  • Most aggressive = > 440 (male), 460 (female)
• To manually calculate QTc:
  • Measure QT interval (start of QRS to end T wave) in lead II or V5-6
  • 1 small box = 40 ms; big box = 200 ms
  • QTc formula
    • If HR 60 = use absolute QT interval
    • If HR 60-100 = Bazett formula (QT / RR interval; RR interval = 60/HR; default machine calculation)
    • If HR outside 60-100 = Framingham or Fridericia formula

• Risk factors for TdP
  • Older age, female
  • Prolonged QTc (best predictor) > 500 ms, congenital long QTS
  • Multiple drugs that prolong QT interval (esp those metabolized by CYP3A4), drugs that inhibit metabolism of QT-prolonging drug (eg CYP3A4 inhibitors eg grapefruit)
  • Previous cardiac adverse effect w/ drugs
  • Other pre-existing heart disease (widened QRS eg Brugada syndrome, syncope, low ejection fraction)
  • Familial long QT syndrome, family history of sudden death
  • Renal disease (electrolyte imbalances, esp hypoK, hypoMg > hypoCa), hepatic disease
  • Anorexia nervosa, chronic heavy EtOH use
• Pharmacological management of agitation in psychotic patients with prolonged QTc
  • Aripiprazole (only AP safe with QTc > 500 ms) > olanzapine, risperidone, quetiapine > asenapine
  • Non-AP (eg if targeting sedation > psychosis tx) = short-acting benzos, trazodone, valproate (not typically used in acute emergencies)
  • Recheck BP + ECG throughout
• D/c offending meds if QTc > 500, > 60 ms from baseline, or 25% increase from baseline (consult cardiology)

• ADT = antidepressant
• Benzo = benzodiazepine
• BD = bipolar disorder
• BID = bipolar I disorder
• BIID = bipolar II disorder
• Fluox = fluoxetine
• DVP = divalproex
• Li = lithium
• LOT = lorazepam, oxazepam, temazepam
• MDD = major depressive disorder
• MDE = major depressive disorder
• Olanz = olanzapine