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Antipsychotics
The document provides an overview of antipsychotics, categorizing them into first and second generations, along with specific medications and their actions, indications, side effects, and management of those side effects. It details dosing instructions, cautions, and monitoring requirements, particularly for clozapine, as well as intramuscular and depot formulations for rapid tranquilization. Additionally, it highlights the metabolic risks associated with antipsychotic use and the importance of regular monitoring to mitigate these risks.
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Antipsychotics
- 1. Antipsychotics K. Kavindya M.Fernando JMJ 1
- 2. Contents • 1st generationantipsychotics • Second generation antipsychotics • Clozapine • Newer 2nd generation antipsychotics • Intramuscular antipsychotics for rapid tranquilization • Depot 1st generation antipsychotics • Depot 2nd generation antipsychotics JMJ 2
- 3. First Generation Antipsychotics Chlorpromazine, Haloperidol,Pimozide, Trifluoperazine JMJ 3
- 4. Action • Dopamine D2post postynaptic receptor antagonists JMJ 4
- 5. Indications • Schizophrenia • Acutemania • Sedation of agitated patients • Agitated depression • Psychotic depression • Chlorpromazine • Used as an antiemetic in palliative care • Treatment of intractable hiccups JMJ 5
- 6. Notes on administration •Tx started at the lowest effective dose • If response is inadequate, • Dose is increased after 2 weeks • Dose can increase upto maximum effective dose • If inadequate response after that, for at least 6 weeks • Change the medication • Antipsychotics can administered once daily JMJ 6
- 7. Side effects Extrapyramidal symptoms Anticholinergic effect Antiadrenergic effect Cardiovascular side effects Hyperprolacten emia Others JMJ7 Dystonia Akathesia Parkinsonism Tardive dyskinesia Neuroleptic Malignant Syndrome Dry mouth Blurred vision Urinary retention Constipation Acute angle glucoma Postural hypotension Ejaculatory delayPostural Hypotension Tachycardia Arrhythmias Sudden death Menstrual abnormalities Galactorrhea Gynacomastia Impotence Drowsiness Seizures Weight gain Skin rash Liver dysfunction Agranulocytosis
- 8. Caution • Renal &hepatic impairment • Epilepsy • Cardiac problems • Pregnancy • Breast feeding • Prostatic hypertrophy JMJ 8
- 9. Management of sideeffects • FGA – cause side effects by • Dopamine blockage in the nigrostriatal pathway • Acute Dystonia • Occur within 1st few hours of commencing treatment • Spasms of the head & neck muscles leading to torticollis • Protrusion of the tongue • Spasm of ocular muscles • Treated with IM benztropine (Anticholinergic) JMJ 9
- 10. Management of sideeffects • Akathisia • Occurs within few days of commencing treatment • It produces feeling of restlessness of lower limbs, • Which causes the patient to move the legs & pace up & down • Reduction of dose or switching to SGA is indicated • Anticholinergic are not effective for tx JMJ 10
- 11. Management of sideeffects • Parkinsonism • Drug induce parkinsonism • If this occurs • Add benzhexol • Reduce dose, or • Witch to SGA JMJ 11
- 12. Management of sideeffects • Tardive dyskinesia 1/2 • Caused by hypersensitivity of dopamine receptors • Generally occurs after a few months of treatment • SGA are less likely to cause tardive dyskinesia • Involuntary movements of the tongue & • Mouth, chewing & sucking movements, • Grimacing & choreoathetoid movements JMJ 12
- 13. Management of sideeffects • Tardive dyskinesia 2/2 • Withdrawal of anticholinergic drugs & • Slow reduction of the antipsychotics • Clozapine is the best substitute • Olanzapine or quetiapine may also be effective • Tardive dyskinesia – often resistant to treatment JMJ 13
- 14. Management of sideeffects • Neuroleptic Malignant Syndrome 1/2 • Rare, potentially fatal side effects • Patients develop • Fever • Muscle rigidity • Fluctuating level of consciousness • Sympathetic overactivity • CPK & WBC are elevated • Antipsychotics- should stopped immediately • Monitor- temp. pulse, BP JMJ 14
- 15. Management of sideeffects • Neuroleptic Malignant Syndrome 2/2 • Supportive management • Best managed in ICU • Specific treatment includes, • Bromocriptine & dandrolene • ECT also known to be effective JMJ 15
- 16. Management of sideeffects • Sedation • Most FGA cause sedation initially, • But become less with continued treatment • Chlorpromazine is more sedating than trifluroperazine or haloperidol • Single night dose will reduce this JMJ 16
- 17. Management of sideeffects • Anticholinergic effects • Can be problematic in the elderly • Chlorpromazine > trifluoperazine or haloperidol • If side effects are troublesome • Discontinue medication • Concurrent anticholinergic medication – benzhexol • Switch to SGA JMJ 17
- 18. Management of sideeffects • Hyperprolactinaemia • Dopamine antagonism in the pituitary hypothalamic axis • FGA more likely to cause this • Can be asymptomatic • Or cause menstrual irregularities, galactorrhoea, gynaecomastia, erectile dysfunction • If prolactin levels are high, change tx to • Olanzapine, quetiapine, aripirazole or clozapine JMJ 18
- 19. Management of sideeffects • Sexual dysfunction • Can occur with both FGA & SGA • Decreased dopamine transmission, hyperprolactenemia, anticholinergic effects & alpha 1 receptor blockage – contribute to sexual dysfunction • Decreased libido, poor arousal • Erectile dysfuction & ejaculatory difficulties • Less sexual problems • Aropiprazole, quetiapine, clozapine JMJ 19
- 20. Second Generation Antipsychotics Amisulpride, Aripiprazole,Olanzapine, Risperidone, Quetiapine, Ziprasidone Clozapine is described in next section JMJ 20
- 21. Action • Antagonism atdopamine D2, D4 receptors • (reduces positive symptoms of schizophrenia) • 5HT 2A antagonists (reduces EPS) • Acts at alpha 1 adrenergic and muscuranic receptors JMJ 21
- 22. Indications • Schizophrenia • Acutemania • Prophylaxis of bipolar affective disorder • Sedation of agitated patients • Agitated depression • Psychotic depression JMJ 22
- 23. Notes on administration •Start treatment with lowest effective dose • If response is inadequate, • Increase the dose after 2 weeks • Dose can be increased upto the maximum effective dose • If inadequate response after that, for at least 6 weeks • Change the medication • Antipsychotics can administered once daily JMJ 23
- 24. Side effects Extrapyramidal symptoms Metabolic Side effects GI disturbances Cardiovascular sideeffects Hyperprolacten emia Others JMJ 24 Dystonia Akathesia Parkinsonism Tardive dyskinesia Neuroleptic Malignant Syndrome Weight gain Diabetes Hyperlipidaemia Metabolic syndrome Diarrhoea Constipation Nausea, vomiting Dyspepsia QT prolongation Arrhythmias Sudden death Menstrual abnormalities Galactorrhea Gynacomastia Impotence Sedation Insomnia Agitation Seizures Blood dyscrasias
- 25. Caution • Renal impairment •Hepatic impairment • Epilepsy • Cardiac problems • Pregnancy • Breast feeding • Blood dyscrasias • SGA may increase the risk of CVA in elderly JMJ 25
- 26. Monitoring • Important asthere is a risk of metabolic syndrome • Weight, BP, plasma glucose & lipid profile • At baseline regular intervals • Weight, plasma glucose, BP • 3 monthly & 3 monthly after that • Lipid profile • 3 monthly and annually after that JMJ 26
- 27. Management of sideeffects • Weight gain • Clozapine & olanzapine- highest risk of weight gain • Amisulpride, aripirazole & ziprasidone • Less likely cause weight gain • Life style modifications are indicated JMJ 27
- 28. Management of sideeffects • Diabetes, hyperlipidemia, metabolic syndrome • Increase cardiovascular mortality & morbidity, because of the increased risk of weight gain & metabolic syndrome • Clozapine, olanzapine- have highest risk • Aripiprazole, quetiapine & ziprasidone • Lowest risk JMJ 28
- 29.
- 30. Action • Dopamine D2antagonist • Reduces positive symptoms of schizophrenia • Serotonin 5HT2A antagonist • Reduces EPS • Binds to • D4 receptors, • Histamine H1 (weight gain & sedation), • Alpha 1 adrenergic & muscuranic receptor antagonist JMJ 30
- 31. Indications • Resistant schizophrenia •Refractory mania JMJ 31
- 32. Notes on administration •Decision to commence should be taken by a consultant • Prior start – do following investigations • Weight • Serum lipids • Fasting blood sugar • Liver function tests • Full blood count • ECG • echocardiogram JMJ 32
- 33. Notes on administration •Admit the patient to hospital to commence clozapine • High risk of hypotension after initial dose • Starting dose – 12.5 nocte • Monitor – • BP, Temp, pulse – in 1st 6 hours • Increase dose slowly by 12.5mg initialy • Then 25 mg later, • With an increase of 50-100mg/week JMJ 33
- 34. Notes on administration •Most respond to dose • 300-450 mg/day • Maximum dose – 900mg • If tx stopped for more than 48 hours, restart at 12.5mg JMJ 34
- 35. Side effects Blood dyscrasias MetabolicSide effects Cardiovascular Others JMJ 35 Neutropenia Agranulocytosis Leukopenia Leucocytosis Eosinophilia Wight gain Diabetes Hyperlipidaemia Metabolic syndrome Hypotension Tachycardia ECG changes Myocarditis Cardiomyopathy Thromboembolism Seizure Sedation Dizziness Hyper salivation Constipation leading to intestinal obstruction
- 36. Contraindications • History ofmyocarditis • Neutropenia • Agranulacytosis • Bone marrow disorders • Paralytic ileus • Avoid during pregnancy and breastfeeding JMJ 36
- 37. Monitoring • As riskof agranulocytosis is highest during the initial period • Monitor FBC weekly till 18 weeks • 2 weekly 18 weeks to 1 year • Monthly thereafter • If patient develops sore throat, fever or infection • Carry out FBC • Monitor weight monthly • Fasting blood s. 3 monthly • Serum lipids 6 monthly JMJ 37
- 38. Management of sideeffects • Neutropenia / agranulocytosis • Total WBC - <3x109/l • Neutrophil count <1.5x 109/l • Eosinophil count > 4 x 109/l • Stop clozapine immediately • Blood counts should be repeated daily JMJ 38
- 39. Management of sideeffects • Hypersalivation • Troublesome side effect • Use minimal effective dose • Add anticholinergics such as • Benzhexol • Hyocine lozengers JMJ 39
- 40. Management of sideeffects • Fever • Can be due to • Infection precipitated by neutropenia • Due to an inflammatory response • May be indicative of myocarditis JMJ 40
- 41. Intramuscular Antipsychotics for Rapid Tranquilization FGA-Chlopramazine, haloperidol, Zuclopenthioxol acetate SGA – Arpiprazole*, olanzapine, Ziprasidone* *Not yet available in SL JMJ 41
- 42. Chlorpromazine – deepIM • Dose- 25 – 50 mg • Every 6-8 hours JMJ 42
- 43. Haloperidol (lactate)- immediate releaseinjection • Dose- 5-10 mg • Can repeat every 4-8 hourly • Maximum dose in 24 hours – 18 mg JMJ 43
- 44. Zuclopenthixol acetate (clopixol acuphase) •Dose- 5-10 mg • Can repeat after 48 hours • Maximum dose 400mg/episode • Maximum 4 injections JMJ 44
- 45. Olanzapine • Dose- 5-10mg • Can repeat after 2 hours if necessary • Maximum daily dose combined oral and parenteral – 20 mg • Maximum 3 injections daily for 3 days JMJ 45
- 46. Aripiprazole • Initially 5.25– 15mg as a single dose (usual dose 9.75mg) • Repeat after 2 hours if necessary • Maximum daily dose combined oral and parenteral -30mg • Maximum of 3 injections/day JMJ 46
- 47. Ziprasidone • Dose 10-20mg •Can repeated 2 hourly • Maximum dose 40 mg • Should not administered for more than 3 consecutive days JMJ 47
- 48. IM antipsychotics forRT • Used only for short period • Oral medication should start after that • After administration, monitor • Level of sedation, temperature, pulse, BP, respi rate • Every 10 minutes for 1st hour • Every ½ hour – until patient is ambulatory JMJ 48
- 49. Side effects • Sameas oral • Dystonic reactions are commoner • Male who have not received apsy previously at a higher risk • Risk of NMS is higher • IM chlorpromazine can cause – sudden drop in BP JMJ 49
- 50.
- 51. Flupenthixol Deconoate • DeepIM into upper outer buttock or lateral thigh • Test dose – 20mg • After 7 days give 20-40mg • Frequency 2-4 weeks • Maximum dose – 400mg/week JMJ 51
- 52. Fluphenazine Deconoate • DeepIM into gluteal muscle • Test dose – 12.5mg • After 4-7 days give 12.5-100mg • Frequency 2-4 weeks • Maximum dose – 100mg/week JMJ 52
- 53. Haloperidol Deconoate • DeepIM into gluteal muscle • Dose 50mg • Frequency 4 weeks • Can increase by 50mg every 4 weeks • Maximum dose – 300mg every 4 week JMJ 53
- 54. Zuclopenthixol Deconoate • DeepIM into upper outer buttock or lateral thigh • Test dose – 100mg • After 7 days give 200-500mg • Frequency 1-4 weeks • Maximum dose – 600mg/week JMJ 54
- 55. Depot antipsychotics dose range Flupenthioxol20-400mg/week Fluphenazine 12.5-50mg/week Haloperidol deconoate 25-300mg /4 weekly Zuclopenthixol deconoate 100-600mg/week Risperidoen long acting 25mg/2 weekly Olanzapine 150-300mg/weeks JMJ 55
- 56.