ANTIPSYCHOTICSANTIPSYCHOTICSSIDE EFFECTSSIDE EFFECTS

Antipsychotics: Side EffectsAntipsychotics: Side Effects

• Neurological (Extrapyramidal) DA-blockNeurological (Extrapyramidal) DA-block• Non-Neurological (Low Potency)Non-Neurological (Low Potency)

• Histaminergic: Sedation, Wt gainHistaminergic: Sedation, Wt gain• Anticholinergic: Perypheral & CentralAnticholinergic: Perypheral & Central• Alpha-Adrenergic: Orthostasis, EKGAlpha-Adrenergic: Orthostasis, EKG• Endocrine-Sexual: PRL, 5-HTEndocrine-Sexual: PRL, 5-HT• Hematologic: AgranulocytosisHematologic: Agranulocytosis• Eye & Skin: retinopathy, photosensitivityEye & Skin: retinopathy, photosensitivity• Seizure threshold: loweredSeizure threshold: lowered• Liver: cholestatic jaundice CPZLiver: cholestatic jaundice CPZ

Extrapyramidal Sx. (EPS)Extrapyramidal Sx. (EPS)

• Acute DystoniasAcute Dystonias

• Antipsychotic-induced Parkinsonism Antipsychotic-induced Parkinsonism

• AkathisiaAkathisia

• Tardive Dyskinesia (TD)Tardive Dyskinesia (TD)

• Neuroleptic Malignat Syndrome (NMS)Neuroleptic Malignat Syndrome (NMS)

Acute DystoniasAcute Dystonias

• Muscle spasm face-neck-trunk-eye-larinxMuscle spasm face-neck-trunk-eye-larinx

• Early in Tx., young malesEarly in Tx., young males

• Dose Related, Tolerance, incidence 50%Dose Related, Tolerance, incidence 50%

• Treatment: Benadryl 50 mg IM (IV 25-50 Treatment: Benadryl 50 mg IM (IV 25-50 for laryngospasm), Cogentin 1-4 mg IM for laryngospasm), Cogentin 1-4 mg IM

• Prevention reduces incidence to 5% Prevention reduces incidence to 5% – Low dose, Low dose, – Benztropine 1 mg / every Haldol 5 mgBenztropine 1 mg / every Haldol 5 mg

Antipsychotic-induced Antipsychotic-induced ParkinsonismParkinsonism

• Incidence 50-75% with high pot.Incidence 50-75% with high pot.

• RigidityRigidity

• Bradikinesia: mask face-gait problemsBradikinesia: mask face-gait problems

• Resting TremorResting Tremor

• Flexed PostureFlexed Posture

• Dif Dx. with flat affectDif Dx. with flat affect

• Tx: Cogentin, Artane 2 mg bid-tid (elder)Tx: Cogentin, Artane 2 mg bid-tid (elder)– Reduces incidence to 5-10%Reduces incidence to 5-10%

AkathisiaAkathisia

• Subjective feeling of restlesnessSubjective feeling of restlesness

• Unable to sit still, pacingUnable to sit still, pacing

• Incidence 20-30%, lower with low doseIncidence 20-30%, lower with low dose

• Dif Dx.: psychosis, agitation, anxietyDif Dx.: psychosis, agitation, anxiety

• Tx: Propranolol 30-90 mg/d (not in Tx: Propranolol 30-90 mg/d (not in asthma or diabetes), Klonopin 1 mg bidasthma or diabetes), Klonopin 1 mg bid

• SSRI Antidepressants cause akathisia tooSSRI Antidepressants cause akathisia too

Tardive Dyskinesia (TD)Tardive Dyskinesia (TD)

• Slow choreo-athetotic movementsSlow choreo-athetotic movements

• Oro-facial musclesOro-facial muscles

• Risk 4% per year of exposureRisk 4% per year of exposure– Risk factors elderly womenRisk factors elderly women

• Risk managementRisk management– document informed consentdocument informed consent

Clozapine low riskClozapine low risk

Neuroleptic Malignant Neuroleptic Malignant Syndrome (NMS)Syndrome (NMS)

• Medical Emerg, mort. 20% (now 4%)Medical Emerg, mort. 20% (now 4%)

• 1. Fever1. Fever >100.4F / 37.5C >100.4F / 37.5C

• 2. Severe EPS2. Severe EPS: lead-pipe/cogwheel rigidity, : lead-pipe/cogwheel rigidity, sialorrhea, oculogyric crisissialorrhea, oculogyric crisis

• 3. Autonomic DysFx3. Autonomic DysFx: BP fluctuations, : BP fluctuations, tachycardia, tachypnea, diaphoresistachycardia, tachypnea, diaphoresis

• Also: Alt. conciousness, delirium, Also: Alt. conciousness, delirium, leukocytosis (>15.000 WBC), CPK > 300, leukocytosis (>15.000 WBC), CPK > 300, seizures, arrithmias, mioglobinuria, ARFseizures, arrithmias, mioglobinuria, ARF

NMSNMS

• Incidence 0.1-1%, (60% of it in 1st 2 wks)Incidence 0.1-1%, (60% of it in 1st 2 wks)

• Risk factors: multiple IM injections, high Risk factors: multiple IM injections, high dose, rapid increase of dose agitation, dose, rapid increase of dose agitation, dehydration, heat, lithium usedehydration, heat, lithium use

• Tx: STOP ALL antipsychotics, also Tx: STOP ALL antipsychotics, also antiemetic (Metoclopramide), antidepr. antiemetic (Metoclopramide), antidepr. AmoxapineAmoxapine

NMS TreatmentNMS Treatment

• Stop ALL AntipsychoticsStop ALL Antipsychotics

• Dif. Dx: fever & deliriumDif. Dx: fever & delirium

• Dantrolene (muscle relax) 1-3 mg/kg/day Dantrolene (muscle relax) 1-3 mg/kg/day NTE 10 mg/kg/dNTE 10 mg/kg/d

• Bromocriptine (DA Agonist) 5 mg tid-qidBromocriptine (DA Agonist) 5 mg tid-qid

• Supportive Tx:Supportive Tx:– IV fluids, antipyretics, cooling blankets, close IV fluids, antipyretics, cooling blankets, close

cardiac & renal monitoringcardiac & renal monitoring

Clozapine: Side EffectsClozapine: Side Effects

• Agranulocytosis (1%)Agranulocytosis (1%)• If WBC<3,000 and ANC<1,500 stop, wait If WBC<3,000 and ANC<1,500 stop, wait

until it returns to 3,500 CBC bi-wkuntil it returns to 3,500 CBC bi-wk• If WBC<2,000 and ANC<1,000 stop & do If WBC<2,000 and ANC<1,000 stop & do

not re-startnot re-start• Do not use with Carbamazepine or other Do not use with Carbamazepine or other

bone marrow suppressorsbone marrow suppressorsANC= Absolute Neutropphil Count, WBC= White Blood Cell, CBC= Complete Blood CountANC = ( % neutrophil + %bands) X WBC

Clozapine: Side EffectsClozapine: Side Effects

• SedationSedation

• Dizziness, orthostatic hypotensionDizziness, orthostatic hypotension

• HypersalivationHypersalivation

• Weight GainWeight Gain

• Lower Seizure ThresholdLower Seizure Threshold

Novel AntipsychoticsNovel Antipsychotics

• RisperidoneRisperidone low EPS at doses <6 mg/d, low EPS at doses <6 mg/d, antidepressant?, elevates PRL, antidepressant?, elevates PRL, [dose 1-8 mg/d][dose 1-8 mg/d]

• OlanzapineOlanzapine positive and negative Sx, low positive and negative Sx, low EPS, sedation, wt gain, mood stabilizer EPS, sedation, wt gain, mood stabilizer [dose: 5-20 mg/day][dose: 5-20 mg/day]

• QuetiapineQuetiapine need bid, low EPS, sedation, need bid, low EPS, sedation, hypotension [dose 200-700 mg/day]hypotension [dose 200-700 mg/day]