01Approach to the Critical Patient/attcp43

Immediate priorities

›High-acuity triggers

›Suicidal ideation or active self-harm urge

›Immediate psychiatric safety assessment

›One-to-one observation

›Severe agitation or heteroaggressive behavior

›De-escalation measures and safe environment

›Consider benzodiazepine for acute control

›Inability to maintain any position for more than a few seconds

›Indicates severe akathisia requiring urgent intervention

›BARS global score 4-5 range

›Paradoxical psychotic worsening after antipsychotic dose increase

›Akathisia misidentified as inadequate antipsychotic effect

›Do NOT increase antipsychotic dose — worsens akathisia

Stabilization targets

›Safety and monitoring bundle

›Continuous vital sign monitoring if initiating propranolol

›Baseline heart rate before propranolol

›Baseline blood pressure before propranolol

›Suicidality screening

›Akathisia associated with suicidal thoughts in 46% and attempts in 38% of affected patients

›First-episode schizophrenia carries highest risk

›ECG if on QT-prolonging antipsychotic

›Haloperidol and ziprasidone prolong QTc

›Obtain QTc before adding further agents

Consult triggers

›Mandatory consultations

›Psychiatry consultation

02History/hx61

Symptom characterization

›Core subjective symptoms

›Inner sense of restlessness

›"Can't sit still" or "need to keep moving"

›Urge to move, especially the legs

›Dysphoric quality

›Patients may report anxiety, tension, or dread rather than movement problem

›Distinguish from pre-existing anxiety

›Movement provides partial relief

›Temporary reduction of inner drive with pacing or leg movement

›Relief distinguishes from anxious rumination

Temporal relationship to medication

›Onset timing

›Acute akathisia onset within hours to days of initiating dopamine-blocking agent

›50% of cases occur within the first month

›Onset up to 6 weeks after initiation qualifies as acute

›Dose escalation trigger

›Rapid titration of risperidone carries HR 6.47 for akathisia

›Any dose increase of FGA can precipitate new episode

›Withdrawal akathisia

›Onset on reducing or stopping antipsychotic

›Persists beyond 6 weeks after dose reduction

Causative agent history

›Offending drug identification

›Highest-risk agents

›Haloperidol — approximately 50% incidence

›First-generation antipsychotics (FGAs) broadly

›Moderate-risk agents

03Physical Exam/exam48

Observation at rest

›Motor restlessness findings

›Rocking while seated

›Rhythmic forward-backward or side-to-side trunk movement

›Cannot be voluntarily suppressed for more than 1-2 minutes

›Leg fidgeting

›Crossing and uncrossing legs repeatedly

›Shuffling or tapping feet

›Inability to remain seated for 2-minute observation period

›Key diagnostic maneuver — ask patient to sit still and observe

›Partial or complete inability to comply supports akathisia

Observation while standing

›Weight-shifting and pacing

›Shifting weight foot to foot

›Rhythmic, repetitive pattern

›Not triggered by external stimulus

›Marching in place

›High stepping in place

›Patient cannot explain why

›Pacing

›Repetitive ambulation without goal

›Patient reports movement provides temporary relief

Neurological examination

›Concurrent extrapyramidal findings

›Tone assessment

›Cogwheel rigidity suggests concurrent drug-induced parkinsonism

›Assess at wrist and elbow bilaterally

›Gait assessment

04Differential Diagnosis/ddx44

Movement disorder mimics

›Restless legs syndrome (ICD-10 G25.81)

›Worse at night — absent in akathisia

›Urge localized to legs with crawling dysesthesia

›Relieved by movement — similar to akathisia

›No temporal relationship to dopamine-blocking medication

›Family history common; responds to dopamine agonists

›Tardive dyskinesia (ICD-10 G24.01)

›Orofacial choreiform movements predominate

›Onset after months to years of antipsychotic exposure

›Antipsychotic dose increase temporarily suppresses TD — key differentiator

›Antipsychotic increase worsens akathisia

›Drug-induced parkinsonism (ICD-10 G21.11)

›Bradykinesia, rigidity, rest tremor predominate

›Can coexist with akathisia

›Responds to anticholinergic therapy

Psychiatric mimics

›Psychotic agitation (ICD-10 F20.0)

›Driven by thought content and delusions

›No stereotyped motor pattern

›No temporal relationship to dose change

›Antipsychotic dose increase may help — worsens akathisia

›Generalized anxiety disorder (ICD-10 F41.1)

›No characteristic rocking or leg movements

›No temporal medication relationship

›Patients with prior anxiety often can distinguish akathisia as qualitatively different

›Manic episode with psychomotor agitation (ICD-10 F31.1)

›Elevated mood, flight of ideas, decreased sleep

05Laboratory Tests/lt40

Iron studies

›Serum iron panel

›Serum iron level

›Lower iron levels associated with akathisia

›Systematic meta-analysis confirms iron homeostasis alteration in akathisia

›Serum ferritin

›Ferritin below 50 mcg/L indicates relative deficiency

›Iron supplementation warranted if deficient

›Total iron-binding capacity (TIBC)

›Elevated TIBC indicates iron deficiency state

›Confirms functional iron availability

Complete blood count

›CBC with differential

›Hemoglobin and hematocrit

›Iron deficiency anemia screen

›MCV low in iron deficiency

›Leukocyte count

›Baseline prior to antipsychotic adjustment

›Clozapine patients require mandatory ANC monitoring

Metabolic panel

›Comprehensive metabolic panel

›Renal function

›Creatinine and eGFR for drug dosing adjustment

›Relevant for renally-cleared antipsychotics

›Hepatic function

›ALT, AST, bilirubin for hepatically-metabolized agents

›Antipsychotic and propranolol metabolism

›Electrolytes

06Diagnostic Tests/dt63

Scoring Systems

›Barnes Akathisia Rating Scale (BARS)

›Most widely validated tool for akathisia severity

›Objective restlessness subscale: 0-3

›Subjective awareness subscale: 0-3

›Subjective distress subscale: 0-3

›Global clinical assessment: 0-5

›Global score interpretation

›0 = absent, 1 = questionable, 2 = mild, 3 = moderate, 4 = marked, 5 = severe

›Score >= 2 indicates clinically significant akathisia

›Administration guidance

›Administer at antipsychotic initiation and each dose titration

›10-minute observation period with patient at rest and standing

›Simpson-Angus Scale (SAS)

›Primarily assesses drug-induced parkinsonism

›Gait, arm drop, shoulder shaking, elbow rigidity, wrist rigidity

›Score > 0.3 indicates parkinsonism

›Use when parkinsonism co-exists with akathisia

›Abnormal Involuntary Movements Scale (AIMS)

›Validated for tardive dyskinesia assessment

›12-item scale covering face, lips, jaw, tongue, extremities, trunk

›Use when tardive dyskinesia is in the differential

MRI

›Brain MRI indications

›Not routinely indicated for akathisia diagnosis

›Akathisia is a clinical diagnosis

›MRI does not confirm or exclude akathisia

›Indications for MRI in atypical presentations

07Disposition/dispo32

Discharge criteria

›Safe for ED discharge

›Akathisia severity criteria for discharge

›BARS global score <= 2 (mild akathisia)

›No suicidal ideation or intent

›Stable psychiatric status without acute decompensation

›Treatment plan requirements

›Oral rescue medication prescribed and tolerated

›Antipsychotic adjustment plan communicated

›Clear follow-up within 48-72 hours arranged

›Caregiver and social factors

›Reliable caregiver or supervision available

›Patient understands return precautions

Admission indications

›Criteria for inpatient level of care

›Psychiatric admission indications

›Active suicidal ideation with plan or intent

›Active heteroaggressive behavior

›Severe akathisia (BARS >= 4) not responding to initial ED treatment

›Medical admission indications

›Inability to tolerate oral medications

›Need for IV beta-blocker or parenteral benzodiazepine

›Significant comorbid medical condition requiring monitoring

›Concurrent psychotic decompensation requiring antipsychotic adjustment in monitored setting

Follow-up planning

›Outpatient follow-up requirements

›Early follow-up timing

›Within 48-72 hours if new rescue medication started

08Treatment/t114

Step 1 — Reduce or eliminate the offending agent

›Antipsychotic dose modification

›Dose reduction of current antipsychotic

›Even 10-20% reduction may relieve akathisia

›Balance against risk of psychotic relapse

›Discontinue antipsychotic polypharmacy

›Identify and remove redundant dopamine-blocking agents

›Antiemetics such as metoclopramide and prochlorperazine are frequent culprits

›Switch to lower-risk antipsychotic

›Quetiapine or olanzapine preferred lower-risk options

›Clozapine lowest akathisia risk

›Switch under psychiatry guidance to prevent psychotic relapse

Step 2 — First-line pharmacotherapy: Beta-blockers

›Propranolol — first-line evidence-based treatment

›Dosing

›Starting dose: 10-20 mg orally twice daily

›Therapeutic range: 20-80 mg/day in divided doses

›Titrate by 10-20 mg/day every 2-3 days based on response

›Mechanism

›Lipophilic beta-blocker with CNS penetration

›Lipophilic agents preferred over atenolol for central effect

›Monitoring

›Heart rate — target HR > 55 bpm

›Blood pressure — avoid systolic < 90 mmHg

›Orthostatic blood pressure at each titration

›Contraindications

›Asthma or reactive airway disease — absolute contraindication

›Decompensated heart failure

›Severe bradycardia (HR < 55 bpm) or AV block

›Insulin-dependent diabetes — may mask hypoglycemic symptoms

Step 2 — First-line pharmacotherapy: Mirtazapine

›Mirtazapine — strongest evidence among 5-HT2A antagonists

›Dosing

›7.5-15 mg orally at bedtime

›May increase to 30 mg/day for refractory symptoms

›Mechanism

›5-HT2A receptor antagonism normalizes dopamine-serotonin balance

›NaSSA class — noradrenergic and specific serotonergic antidepressant

›Evidence

›Network meta-analysis 2024: mirtazapine among best-ranked treatments

›Schizophrenia Bulletin 2026 network meta-analysis confirms efficacy

›Side effects

›Sedation — may be beneficial for distressed patients

›Weight gain with long-term use

›Dry mouth

Step 2 — Second-line pharmacotherapy: Benzodiazepines

›Clonazepam — preferred benzodiazepine for akathisia

›Dosing

›0.5 mg orally twice daily initially

›Therapeutic range: 0.5-2.5 mg/day in divided doses

›Indication

›Primarily for subjective distress component

›Useful adjunct when dysphoria and anxiety are prominent

›Precautions

›Sedation risk — monitor driving ability

›Dependence risk with long-term use

›Respiratory depression risk with concurrent opioid use

›Avoid in patients with substance use disorder history unless supervised

Step 2 — Second-line pharmacotherapy: Anticholinergics

›Biperiden — best-evidenced anticholinergic for akathisia

›Dosing

›2-6 mg/day orally in divided doses

›6 mg/day based on network meta-analysis evidence

›Mechanism

›Muscarinic M1 receptor blockade restores dopamine-acetylcholine balance

›Evidence

›Network meta-analysis: biperiden favored over benztropine for akathisia specifically

›Side effects

›Dry mouth, urinary retention, constipation, blurred vision

›Cognitive impairment — use cautiously in elderly

›Paradoxical worsening of tardive dyskinesia if misdiagnosis occurs

›Benztropine — alternative anticholinergic

›Dosing

›0.5-2 mg orally or IM twice daily

›IM route available for acute ED use

›Less studied than biperiden specifically for akathisia

Step 3 — Third-line and adjunctive agents

›Vitamin B6 (pyridoxine)

›Dosing

›600-1200 mg/day orally

›Well-tolerated with favorable safety profile

›Evidence

›Moderate evidence from controlled trials

›Considered when first-line agents fail or are contraindicated

›Clonidine

›Dosing

›0.05-0.3 mg/day orally in divided doses

›Alpha-2 agonist mechanism

›Use

›Third-line option for refractory akathisia

›Monitor for hypotension and rebound hypertension on discontinuation

›Cyproheptadine

›Dosing

›4 mg orally every 12 hours

›5-HT2A antagonist with antihistamine properties

›Evidence

›Double-blind RCT 2026: NNT approximately 2 for acute akathisia

›Emerging agent with promising early data

›Trazodone

›Dosing

›50 mg orally at bedtime

›5-HT2A antagonism mechanism similar to mirtazapine

›Evidence

›Moderate evidence; sedation may be beneficial adjunct

Iron replacement

›Iron supplementation if deficient

›Target ferritin > 50 mcg/L

›Oral ferrous sulfate 325 mg orally twice daily with meals

›Systemic meta-analysis confirms association between low iron and akathisia

›Duration

›Continue until ferritin normalized and reassess akathisia severity

›Recheck iron studies in 4-6 weeks

What not to do

›Treatment errors to avoid

›Do NOT increase antipsychotic dose for akathisia

›Creates vicious cycle of worsening restlessness

›Most dangerous management error

›Do NOT stop antipsychotics abruptly without psychiatric guidance

›Withdrawal akathisia can occur

›Psychotic relapse risk

›Avoid anticholinergics as sole treatment if diagnosis is uncertain

›Will worsen tardive dyskinesia if that is the correct diagnosis

09Special Populations/sp73

Pregnancy

›Pregnancy-specific considerations

›Risk-benefit analysis of antipsychotic continuation

›Untreated psychosis poses greater risk to mother and fetus than most antipsychotics

›Involve obstetrics and psychiatry in all decisions

›Antipsychotic safety in pregnancy

›All antipsychotics cross the placenta

›Quetiapine and olanzapine preferred due to lower EPS risk in pregnancy

›Haloperidol and high-potency FGAs carry higher akathisia risk

›Treatment modifications in pregnancy

›Propranolol use in pregnancy

›Category C — associated with fetal bradycardia and IUGR

›Short-term use for severe akathisia may be acceptable with fetal monitoring

›Avoid in third trimester if possible

›Benzodiazepine use in pregnancy

›Clonazepam: Category D — risk of neonatal withdrawal and respiratory depression

›Reserve for severe refractory akathisia after first trimester

›Vitamin B6 in pregnancy

›Safe and preferred adjunctive option in pregnancy

›600-1200 mg/day — well-established safety profile in pregnancy (used for nausea)

›Mirtazapine in pregnancy

›Limited data but generally considered low risk

›Category C — monitor neonatal adaptation syndrome

Geriatric

›Age-related considerations

›Altered pharmacokinetics in older adults

›Reduced hepatic and renal clearance prolongs drug half-lives

›Start all agents at lowest doses (start low, go slow)

›Fall risk

›Akathisia itself increases fall risk from psychomotor agitation

›Propranolol increases fall risk from orthostatic hypotension

›Benzodiazepines markedly increase fall and fracture risk

›Drug-specific geriatric concerns

›Propranolol in older adults

›Use lower starting doses — 10 mg orally twice daily

›Orthostatic hypotension monitoring essential

›Higher risk of bradycardia at standard doses

›Anticholinergics in older adults

›Avoid if possible — Beers Criteria lists anticholinergics as potentially inappropriate

›Urinary retention, delirium, constipation, and cognitive impairment risks

›If required, use lowest effective dose for shortest duration

›Benzodiazepines in older adults

›Avoid per Beers Criteria — high risk of falls, cognitive impairment, delirium

›If essential, lorazepam 0.5 mg preferred over clonazepam

›Antipsychotic selection in older adults

›Avoid high-potency FGAs (haloperidol) when possible

›Higher EPS and akathisia risk in older adults

›Quetiapine and olanzapine preferred for lower EPS burden

›Dementia-related psychosis — note FDA black box warning for antipsychotic use

Pediatrics

›Pediatric akathisia considerations

›Incidence and recognition challenges

›Akathisia in children may present as behavioral agitation, school refusal, or separation anxiety

›Children may lack language to describe inner restlessness

›Collateral from parents and teachers essential

›Common pediatric triggers

›Metoclopramide for gastroparesis or nausea — common pediatric cause

›Second-generation antipsychotics for autism spectrum disorder behavioral symptoms

›Aripiprazole increasingly used in children with autism — moderate akathisia risk

›Dosing in pediatric patients

›Propranolol in children

›Weight-based dosing: 0.5-1 mg/kg/day orally in 2-3 divided doses

›Maximum 4 mg/kg/day

›Monitor heart rate closely — bradycardia risk

›Benzodiazepines in children

›Lorazepam 0.05-0.1 mg/kg IV/IM for acute severe agitation

›Avoid long-term use in children

›Vitamin B6 in children

›Safe and preferred option for mild-to-moderate pediatric akathisia

›Dose: 10-15 mg/kg/day

›Anticholinergics in children

›Benztropine 0.02-0.05 mg/kg/dose IM or IV for acute dystonia or akathisia

›Maximum single dose 2 mg

›Barnes Akathisia Rating Scale in children

›BARS validated for patients 7 years and older

›Modified observation techniques required for younger children

10Background/b87

Epidemiology

›Prevalence and incidence

›Overall akathisia prevalence

›20-50% of patients on antipsychotics develop akathisia depending on agent

›Reported incidence up to 75% with high-potency FGAs in some series

›Underdiagnosed in clinical practice

›First-generation antipsychotic rates

›Haloperidol — approximately 50% incidence

›Chlorpromazine — lower due to lower D2 affinity

›Second-generation antipsychotic rates

›Aripiprazole and risperidone — moderate risk

›Olanzapine — approximately 4-5% incidence

›Quetiapine and clozapine — lowest rates

›Temporal patterns

›Acute akathisia — onset within hours to 6 weeks of initiation or dose increase

›50% of cases within the first month

›Most common form encountered in ED

›Chronic akathisia — persists beyond 3 months

›Tardive akathisia — onset after months to years; may persist after drug withdrawal

›Withdrawal akathisia — onset within 6 weeks of dose reduction or discontinuation

›Clinical impact

›Medication nonadherence — leading cause of antipsychotic nonadherence

›Suicidal ideation in up to 46% of patients with akathisia

›Suicide attempts in up to 38% of patients with akathisia in one study

›Associated with aggression, heteroaggression, and prolonged hospitalization

Pathophysiology

›Dopaminergic mechanism

›Core mechanism: D2 receptor blockade in mesolimbic pathways

›Dopamine receptor occupancy > 80% associated with EPS including akathisia

›Mesolimbic pathway — reward and motivational circuits

›Mesocortical pathway involvement contributes to dysphoric component

›Nigrostriatal versus mesolimbic dissociation

›Parkinsonism predominates with nigrostriatal blockade

›Akathisia has both striatal and limbic contributions

›Serotonergic contribution

›5-HT2A receptor antagonism reduces akathisia risk

›Explains why SGA agents with 5-HT2A blockade have lower akathisia rates

›Basis for mirtazapine, trazodone, and cyproheptadine efficacy

›SSRI-induced akathisia

›Serotonin-mediated inhibition of dopaminergic neurons

›Especially in mesolimbic circuit

›Noradrenergic mechanism

›Beta-adrenergic hyperactivity in basal ganglia implicated

›Explains efficacy of lipophilic beta-blockers (propranolol)

›CNS penetration required — peripheral beta-blockers less effective

›Locus coeruleus noradrenergic dysregulation contributes

›Iron deficiency mechanism

›Iron is a cofactor for tyrosine hydroxylase — rate-limiting enzyme in dopamine synthesis

›Low iron impairs dopaminergic neurotransmission

›Increases vulnerability to D2-blocking agent effects

›Reduced D2 receptor density with iron deficiency

›D2 receptors in striatum reduced in iron-deficient states

›Shared mechanism with restless legs syndrome

›Classification subtypes

›Acute akathisia — within 6 weeks; reversible with dose reduction

›Chronic akathisia — persists beyond 3 months despite dose reduction

›Tardive akathisia — onset after prolonged exposure; may be irreversible

›Withdrawal akathisia — emerges on dose reduction or discontinuation

Therapeutic Considerations

›Treatment hierarchy evidence base

›2024 JAMA Network Open network meta-analysis

›Most comprehensive comparative evidence to date

›Propranolol and mirtazapine among highest-ranked treatments

›Vitamin B6 had favorable safety-efficacy profile

›2026 Schizophrenia Bulletin network meta-analysis

›Confirmed propranolol and serotonergic agents as preferred

›Benzodiazepines effective but limited by adverse effect profile

›B-CALM mnemonic for treatment agents

›Beta-blockers (propranolol)

›Clonazepam/benzodiazepines

›Anticholinergics (biperiden, benztropine)

›cLonidine

›Mirtazapine

›Antipsychotic switching considerations

›Cochrane review 2025: switching evidence for non-responsive schizophrenia

›Switching carries risk of psychotic relapse during transition

›Cross-titration preferred over abrupt switch

›Quetiapine, olanzapine, or clozapine as lower-akathisia targets

›Canadian Journal of Psychiatry 2018 guidelines

›Systematic assessment with BARS recommended at baseline and follow-up

›BARS-guided treatment adjustments

›Prevention strategies

›Akathisia prevention

›Use lowest effective antipsychotic dose

›Avoid rapid titration — especially risperidone

›Screen iron status before initiating antipsychotic therapy

›Prefer SGA agents with 5-HT2A antagonism for vulnerable patients

›Prophylactic beta-blocker not routinely recommended

›Insufficient evidence for prophylactic use

›Targeted treatment preferred once akathisia develops

11Patient Discharge Instructions/pdi35

copy discharge instructions

›What is akathisia

›Akathisia is a medication side effect causing inner restlessness and the urge to move

›It is caused by the medication you are taking, not a worsening of your condition

›It is treatable and typically improves with medication adjustment

›Common symptoms to expect during recovery

›Restlessness and urge to move may take a few days to begin improving

›The new medication we gave you should help within 24-48 hours

›Do not stop your antipsychotic medication without speaking to your doctor first

›Medication instructions

›Take the prescribed rescue medication exactly as directed

›Propranolol: take with food, do not stop suddenly

›Clonazepam: do not drive or operate heavy machinery while taking

›Mirtazapine: take at bedtime due to sedation

›Do not change your antipsychotic dose on your own

›Your psychiatrist will guide dose adjustments

›Stopping abruptly can cause withdrawal and worsening symptoms

›Activity and diet

›Movement can temporarily relieve symptoms — gentle walking is encouraged

›Restlessness should not prevent you from resting with treatment

›Iron-rich foods if iron deficiency was identified

›Red meat, leafy greens, legumes, fortified cereals

›Take iron supplements with vitamin C to improve absorption

›Reduce caffeine intake — may worsen inner restlessness

›Return to emergency department immediately for

›Return precautions

›Thoughts of harming yourself or others

›Worsening agitation that is uncontrollable despite medication

12References/r39

Guidelines and key sources

›Factor SA, Burkhard PR, Caroff S, et al.

›Recent Developments in Drug-Induced Movement Disorders: A Mixed Picture

›Lancet Neurology 2019; PMID 31279747

›Pringsheim T, Gardner D, Addington D, et al.

›The Assessment and Treatment of Antipsychotic-Induced Akathisia

›Canadian Journal of Psychiatry 2018; PMID 29685069

›Gerolymos C, Barazer R, Yon DK, et al.

›Drug Efficacy in the Treatment of Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-Analysis

›JAMA Network Open 2024; JAMA Network Open 2024.1527

›Furukawa Y, Imai K, Takahashi Y, Efthimiou O, Leucht S.

›Comparative Efficacy and Acceptability of Treatment Strategies for Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-Analysis

›Schizophrenia Bulletin 2026; PMID 38869177

›Thippaiah SM, Fargason RE, Birur B.

›Struggling to Find Effective Pharmacologic Options for Akathisia? B-CALM!

›Psychopharmacology Bulletin 2021; PMID 34421146

Landmark trials and key studies

›Barnes TR.

›The Barnes Akathisia Rating Scale — Revisited

›Journal of Psychopharmacology 2003; PMID 14870947

›Schoretsanitis G, Nikolakopoulou A, Guinart D, Correll CU, Kane JM.

›Iron Homeostasis Alterations and Risk for Akathisia in Patients Treated With Antipsychotics

›European Neuropsychopharmacology 2020; PMID 32444336

›Kalniunas A, Chakrabarti I, Mandalia R, Munjiza J, Pappa S.

›The Relationship Between Antipsychotic-Induced Akathisia and Suicidal Behaviour: A Systematic Review

›Neuropsychiatric Disease and Treatment 2021; PMID 34887662

›Shams-Alizadeh N, Maroufi A, Rahmani K, et al.

›Evaluating the Effectiveness of Cyproheptadine on Acute Neuroleptic-Induced Akathisia: A Double-Blind RCT

Evidence & Review

Evidence & Review