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It is a term used to describe a group of severe mental illness characterized by
hallucination, delusions, extreme abnormalities of behavior including marked over-
activity, retardation, catatonia and usually a lack of insight.

Functional psychoses: Schizophrenia and affective disorders, Schizo-affective
mood disorders (bipolar).
Organic psychoses: secondary to pre-existing medical condition.
May be due to illicit substance use…

Examples of drugs causing psychosis
Cocaine, Amphetamine, Levodopa, Methyl phenidate, Ketamine, Cannabinoids,

Anti-psychotic drugs
These are group of drugs used to treat psychiatric disorders characterized by
disturbed thought and behavior-primarily Schizophrenia.

Note: These drugs are notcurative and do not eliminate the chronic thought
disorder but they often decrease the intensity of hallucinations, delusions and
permit the person with Schizophrenia to function in a supportive environment.

A hallucination is a perception in the absence of apparent stimulus that has qualities
of real perception. It may affect all the five senses. Auditory hallucination is very
common while visual hallucination is abit rare.

It is a wrong or mis-interpreted perception of a sensory experience.

A false belief that cannot be dislodged even by solid proof of contradictory evidence
or by reasoning the subject.

Bizarre delusion: very strange and completely implausible.
Non-bizarre delusion: A delusion though false but is at least possible.
Delusion of grandiosity: eg the patient is King, Queen, God….
Delusion of thought insertion: belief that another person thinks through the mind of
the person.

It comes from the Greek word meaning “split” and “mind”.
People with Schizophrenia are split off from the reality and cannot distinguish
between real and not real. It is the most common and debilitating form mental


pre-natal poor nutrition. Positive symptoms: Hallucination (auditory). per-natal hypoxia.  Excessive limbic dopaminergic activity plays a role in psychosis.  Post-mortem studies of Schizophrenia subjects have reported increased dopamine levels and D2-receptor density in nucleus accumbens. persecution. Epidemiology Schizophrenia occurs in 1% of the population world-wide. Pathogenesis 1. Blunted affects. birth rank. IBRAHIM Three major symptoms of Schizophrenia: 1. flattening of emotional responses. 2 . Glutamate hypothesis Abnormal concentration of glutamate in hippocampus and pre-frontal cortex (PFC) occurs in Schizophrenia subjects. cognitive control of behavior.  Diminished cortical and hippocampal dopaminergic activity underlie cognitive impairment and negative symptoms of Schizophrenia. Paranoid…) Catatonia (purposeless motor activity and immobility). It has a strong genetic predisposition. caudate and putamen. Negative symptoms: social isolation. It usually affects during late adolescence or early adulthood. 2. 2. Note: The main neurotransmitters involved in the pathogenesis of Schizophrenia are dopamine and glutamate. Anhedonia (Inability to derive pleasure) impoverished speech (alogia: absence of words). Cognitive symptoms: deficit in working the memory. season of birth. 3. advanced paternal age. Dopamine Hypothesis of Schizophrenia (no longer considered adequate to explain all aspects of Schizophrenia but enough to understand positive and negative symptoms). Risk factors Environmental factors: prenatal exposure to viral infections. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. delusions (Gradiosity.

moderate sedative effects. Butyrophenones  Benperidol  Haloperidol (3-5 mg. C. IBRAHIM Anti-psychotics First generation anti-psychotics  Acts predominantly by blocking the dopamine D2-receptors in the brain. ------------------ - Group II Fewer EPS compared to Group I and group III. Phenothiazines: 3 groups Group I They are characterized by profound sedation and moderate anti-muscarinic and Extra pyramidal side-effects. Dru Fluphenazine Perphenazine Prochlorperazi Tri gs decanoate ne fluoperazin e Dos 25 mg IM q 2 weeks Oral: 75-100 5-10 mg/day e mg/day IM: 12. max: 30 mg/day). 2-3 times/day.5-25 mg TDS B. more EPS compared to GP I and II. Drugs Pericyazine Pipotiazine Mesoridazine Dose 15-75 mg/day IM at 4 weeks interval 50-400nmg/day Group III Fewer sedative and anti-muscarinic effecs. depot preparation also available. A. Diphenyl butyl piperidines 3 . EPS. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. Drugs Chlorpromazine levomeproma Promazine zine Dose/ro Oral/IM/PR 25-100 mg/day 100-200mg ute Initial oral dose: 25 mg TDS (75-300 QID mg/day) IM: 25-500 mg q 6-8 hours PR: 100 mg q 6-8 hours. Remarks Limited use nowadays -------------------.

100mg tabs. Thioxanthene  Thiothixene Low potency anti-psychotics Chlorpromazine Prochlorperazine Thioridazine Moderate potency Molindone: 15-20 mg/day High potency Anti-psychotics Fluphenazine Haloperidol Pimozide Flupenthixol (can cause excitation and gynaecomastia) Zuclopentixol Sulpiride: 200-400 mg BD (maximum: 800 mg/day) Atypical Anti-psychotics/second generation anti-psychotics 1. Postural hypotension. 5. It has high affinity for D4 receptor. Aripiprazole Dose: 15 mg OD (max: 30 mg/day). Dose: initially 12. negligible effect on QT interval and least likely to cause hyperglycemia. IBRAHIM  Pimozide: 2-20 mg/day ( removed due to high risk of QT elongation). Piperazine  Fluphenazine E.  Least risk of EPS. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T.  Unlike other anti-psychotics. Clozapine It is a di benzo-diazepine derivative.5-25 mg /day. -adrenoceptor and muscarinic receptors. maintenance of 300-600 mg by gradual titration. 10. collapse Seizure 3-5% Myocarditis and cardiomyopathy. D. 4 . 5 HT2A. it lowers prolactin level and also cause nausea. 2. Main adverse effects: Agranulocytosis (WBC initially to be monitored every week for 2 months then greater spacing). D2. 25. it also blocks D1. 15 g tabs No weight gain D2-partial agonist with weak 5 HT1A partial agonism.

H1 receptor antagonist.5-10 mg/day. Approved for treatment of Bipolar disorder. Short T1/2: 6 hours Dose: 300-450 mg/day (max:750 mg/day). 7. 5. 5HT2 antagonism. Examples of anti-psychotic drugs available as Depot preparations Protiazinepalmitate: Im every 4 weeks-50 ng/ml Fluphenazinedecanoate: 25 mg deep IM q 2 weeks Haloperidol decanoate: 100 mg deep IM q 4 weeks Flupentixol: 40 mg IM q 2 weeks Zuclopentixol: 200 mg IM q 2 weeks Paliperidonepalmiatte. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. Amisulpride Selective dopamine antagonist with high affinity for mesolimbic D 2 and D3 receptors. D4. D2. 8. . 3. 4. 5HT1A partial agonist. 5. Ziprasidone. Olanzapine  It is a thiene-benzodiazepine derivative.receptor. Quetiapine It is D1. IBRAHIM Risk of weight gain and hyperglycemia:+++ Note: it is the only agent indicated to reduce risk of suicide. Dose: 400-800 mg daily. Zotepine. start with 50 mg/day and titrate up. Dose: 6 mg OD. Dose: 10-20 mg/day. Iloperidone. Remoxipride. 10 mg tabs.  Dose: 5-10 mg/day.  T1/2: 33 hours. Depot preparation available. Lurasidone. Practically no EPS Other drugs Ziprasidone. 5HT2. dose range: 0. Aripiprazole… 5 .  Weight gain/ hyperglycemia: +++  It is associated with the greatest risk of stroke in elderly patient. Sertindole (cause nasal congestion and risk of ventricular arrhythmia). D2. Risperidone. 6. Risperidone Best effects seen at doses less than 6 mg/day. Paliperidone It is the active metabolite of Risperidone.  It causes D1. Asenapine It is a dibenzo-oxepriopyrrole Available for oral and sublingual use.

6. adrenergic and histaminergic receptors. All the older (first generation) and most of the newer neuroleptics block dopamine receptors in the brain and its periphery. IBRAHIM Advantages of Atypical over typical anti-psychotics.D4. Risk of agranulocytosis with Clozapine. 3. Less incidence of hyperprolactinemia (Aripiprazole actually decreases the serum prolactin level). D3. Sexual dysfunction and skin problem are less. Disadvantages of second generation anti-psychotics 1. -receptors Olanzapine and Risperidone: 5HT2A…. D2. Anti-psychotic actions  Decreases the positive symptoms of Schizophrenia by causing D 2- receptor blockade in mesolimbic system of brain. 5HT2. particularly 5HT2A receptors. 1. Absence or marked reduction in occurrence of EPS. often exciting neurone. 3. 2. D5) D1andD5 receptors activate adenylyl cyclase. 1. Better tolerance and compliance to the drug. Clinical efficacy of typical neuroleptics is related to their ability to block D2receptors on mesolimbic system of the brain. these drugs also block muscarinic. D2. However. 7. Atypical anti-psychotics have been found to have neuro-protective action also. 6 . Dopamine receptors: 5 types (D1. D2. 2. D4. High risk of weight gain and hyperglycemia. Increase incidence of cardiovascular disorders. Pharmacological actions Anti-psychotics actions are due to blockade of dopamine receptors and serotonin receptors. Note: Clozapine and Risperidone cause substantial blockade of -receptors which may account for their beneficial effect on negative symptoms of Schizophrenia. muscarinic. 4. Serotonin-Blocking activity in brain Most of the newer atypicalagents exert part of their action by inhibition of 5HT receptors. Able to decrease the negative symptoms of Schizophrenia. D3. Mechanism of action 1. H1. D4 receptors: inhibit adenylyl cyclase and mediate membrane K + channel opening leading to neuronal hyperpolarization. 5. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. Atypical anti-psychotics have more affinity for other dopamine receptors. Examples: Clozapine: D1. typical anti- psychotics decrease only the positive symptoms. 2. Little effect or not effect on QT interval.

Olanzapine. 7. Blockade of Dopamine receptors in the Nigrostriatal pathway leads to EPS. the consequence is gynaecomastia. They lead to adverse effects such as blurring of vision. All anti-psychotic medications are highly lipophilic. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. 5. dry mouth (except clozapine which despite having anti- muscarinic action causes hypersalivation). Dystonia (sustained contraction of muscles leading to twisting and distorted posture).. Parkinsonism. which is characterized by Akathisia. highly membrane bound or protein bound and accumulates in the brain and other tissues with rich blood supply such as the lungs. constipation. 2. 3. Blockade of dopamine receptors in Tubero-infundibular pathway leads to hyperprolactinemia which in turn leads to galactorrhoea. menstrual disturbances in females. Blockade of dopamine receptors in Medullary peri-ventricular pathway is involved in eating behavior and that of Incerto-hypothalamic pathway is involved in copulatory behavior in animal. neuroleptics shows variable absorption which is unaffected by food in most cases (except Ziprasidone and Paliperidone whose absorption increase with food) Phenothiazine are erratically absorbed after oral administration but its absorption is good following intramuscular administration. Anti-emetic effects Most anti-psychotics (except Aripiprazole and Thioridazine) have anti emetic action which is mediated by D2-receptor blockade in the CTZ. 4. IBRAHIM  Atypical anti-psychotics such as Clozapine improve the negative symptoms also. Dopamine released by these neurons physiologically inhibit prolactin secretion from the anterior pituitary.  Calming effects and reduction in spontaneous physical movements. 6. Pharmacokinetics 1. Chlorpromazine. Anti-muscarinic effects Common with Thioridazine. infertility. Clozapine. 3. Volume of distribution varies from 7-20 L/Kg 7 . Note: Anti-psychotics take about 2-4 weeks to show optimum action. Tardive dyskinesia. Note: Atypical anti-psychotics have less risk of causing EPS. Blockade of α-1 adrenergic receptors Leads to orthostatic hypotention. After oral administration. urinary retention. impotence and infertility. 2. In males.

IBRAHIM 4. Schizo-affective disorders. Example Fluphenazine decanoate: 2-3 weeks. 8 . CYP3A4). Examples: Flupentixol decanoate. 5. Examples: Long-acting: t1/2 Haloperidol: 18 hours t1/2 olanzapine: 33 hours t1/2 Aripiprazole: 3 days Short-acting t1/2 Quetiapine: 6 hours t1/2 Ziprasidone: 8 hours Some depot preparation are also available for slow release and their duration of action varies from 2-4 weeks. Depot preparation can also be used for maintenance when compliance with oral treatment is a problem. Schizophrenia Note: catatonic Schizophrenia is best treated managed by IV anti-psychotics.5 mg/day. For short term adjunctive management of severe anxiety associated with psychomotor agitation. Psychotic depression 5. 3. Deviant social and sexual behavior: benperidol 0. 6. Other uses 1.  Vertigo in Meniere’s disease. They are metabolized to many different substances by CYP 450 system (particularly CYP2D6. Indications Psychiatric 1. Alzheimer 7. 2.25-1. violence or impulsive behavior. 4. Senile psychosis. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. excitement. Plasma t1/2 of most anti-psychotics varies from 15-30 hours. Anti-emetic  To treat nausea and vomiting or to prevent nausea and vomiting which is drug induced. Manic phase of bipolar disorder and in hypomania. CYP1A2. IV haloperidol for rapid control of symptoms followed by Quetiapine or Chlorpromazine or Riseridone along with mood stabilizers.

5-1. Clozapine is the only Atypical agent indicated to reduce risk of suicide. 0. Intractable hiccups Chlorpromazine: 10-25 mg oral q 4-6 hourly (25-50 mg IM) Haloperidol: 1. 9. Olanzapine Clozapine: 50-600 mg/day Quetiapine: 50-600 mg/day Tetrabenazine and baclofen are also used in its management. Huntington’s chorea Haloperidol/Risperidone (2-8 mg/day). Pain control (in painful terminal illness) Levopromazine 12. Pruritus Trimeprazine is useful because of its high anti-histaminic and sedative action. 5. IBRAHIM  Labyrinthitis  Migraine Drugs used: Prochlorperazine: 5-20 mg/day (stemetil) Haloperidol: 1-2 mg IM/IV Levopromazine: 6 mg oral/sc Benzquinamide 2. Autism They decrease the disruptive behaviour and irritability. They reduce emotional response to pain and potentiate some central effects of narcotic analgesics.5 mg Olanzapine/Risperidone 8.5 mg tds 3. 4.Anxiety disorders Obsessive Compulsive disorder. Haloperidol + diamorphine Sc infusion. OCD and Post Traumatic Stress Disorder. 10. PTSD Drug used: olanzapine/Risperidone/Quetiapine along with SSRI 9 . Risperidone: 0. As component of Neuroleptanalgesia (droperidol and Fentanyl)and Neuroleptanaesthesia (droperidol+ Fentanyl+nitrous oxide) 6.25 mg (<25 kg). Acute “behavioural emergencies” such as violent patients with range of psycho-pathologies including mania and toxic delirium. Gille de la Tourette Syndrome Haloperidol: 0.5-3 mg/day (>25 kg) Aripiprazole: 30 mg/day. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. 7.5mg-50 mg. Sc infusion every 24 hours.

Aripiprazole (10-15 mg/day to max 30mg/day). if given early. 5. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T.such as Reserpine. Refractory cases of choreo-athetoid or choreatic tardive the first generation dyskinesia can of anti-psychotics be treated by andcatecholamine occurs after several months (dopamine) to years depletors of treatment. 6. periodic follow up and reassess therapy.pyramidal system. 10 General measures Encourage the patient. Elimination of stimulants or even on withdrawal of the causative agent. . with It is most common 3. rigidity. Other drugs used to increase GABA ergic Transmission are: Muscimol (5-9 mg/day). Promethazine (avomine): motion sickness. Ziprasidone. Withdrawal of the offending drug. psychotherapy. tremors.125 mg/day and escalated slowly up to 6 mg/day or use Tetrabenazine initially with 12. Management: respond to centrally acting anti-cholinergics (Biperiden 2-12 mg. “pseudo depression” with older anti-psychotics due to drug induced akinesia (respond to anti-parkinson treatment). clozapine. Parkinsonism: bradykinesia. Olanzapine (5-10 mg/day). IBRAHIM 11.Shock (off-label use) 12. Replace typical anti- Treatment: centrally psychotics byacting anticholinergic atypical anti-psychotics+ such clonazepam. benztropine 1-6 mg) and H1-antagonist with significant anticholinergic action such as diphenhydramine. provide good nourishing diet. Quetiapine (300-750 mg/day).TCA and Anti-cholinergics drugs.Hypertension reaction complicating MAO inhibitors and TCA therapy (off label use) Prophylactic uses 1. ii Akathisia (uncontrollable restlessness) along with dystonic reaction (torticollis/retrocollis). There is difficulty due to dose dependent sedation and orthostatic hypotension with these drugs. The treatmentItincorporates: occurs after large initial dose. olanzapine. 1. Amisulpride (800-1200 mg/day). a small dose of 0. They increase GABA concentration in extra. Droperidol: prevention and treatment of post-operative nausea and vomiting 2. reduces voluntary movements. Extrapyramidal symptoms.ergic activity. 4. iii Tardive dyskinesia Diazepam 10-20 mg/day (Gradual titration if needed) can be used to enhance GABA. Least with Quetiapine. Clonazepam (1-8 mg/day) and Valproic acid (750-3000 mg/day). It is the most serous reassess manifestation the treatment of EPS and is usually irreversible periodically.5 mg/day up to 200 mg/day. 2. After discontinuation. Vit E. 2. risperidone (4-10 mg/day). EPS Due to blockade of Nigrostriatal pathway Common with first generation anti-psychotics. as clozapine (50 mg/day). physiotherapy. Adverse effects All anti-psychotics produce adverse effects that are extension of their pharmacological action. Baclofen (40-80 mg/day). Use of Lecithin is indicated as it helps in providing choline with increasing acetylcholine in striatum. mask facies. EPS is characterized by: i.

Toxic confusional stae 5. 3. Cooling blankets and antipyretics can be used to control temperature.Iv. fever. Dopaminergic agonists Bromocriptine: Dosage very much from 2. Direct acting skeletal muscle relaxant Dantrolene: 1mg/kg.5-5 mg TDS. The drug Dantrolene is hepatotoxic although rarely does it cause liver 11 damage but liver function isto be monitored during therapy. unstable BP. The most important intervention is to discontinue all antipsychotics. Neuroleptic Malignant Syndrome Characterized by extreme form of rigidity. Every patient therapy is to be individualized. to be increased up to 10mg/kg. Patients should receive circulatory and ventilatory support as needed. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. Treatment of complications Hemodialysis: For preventing renal failure to occur from rhabdomyolysis a . it can occur as fast as the first week of therapy or after Treatment: months to years of treatment. myoglobinemia. the suitable dose is 5-15mg/day to maximum 35mg/day. III. 6. symptoms will resolve in 1-2 weeks. 1. It can be given concurrently with the dopaminergic agonists. use supportive care aggressively. 4. Sedation and drowsiness 4. II. Other drug used is Amantadine 100-300mg/day (D1/D2 agonist). 2. After short term therapy oral medication with Dantrolene is started using 25mg/day to 100mg QID depending upon the nature and duration of the disease. Benzodiazepines: Diazepam 5-10mg/day. 5. IBRAHIM 3. They reduce recovery time in neuroleptic malignant syndrome and are beneficial in managing agitated and hyperactive patients. During the course of neuroleptic malignant syndrome.. Supportive measures are aimed at preventing further complications and maintaining organ function. I. IV initially. Aggressive fluid resuscitation and alkalization of urine can help prevent acute renal failure and enhance excretion of muscle breakdown products. 7. In most cases. Neuroleptic malignant syndrome precipitated by long-acting depot injections of antipsychotics can last as long as a month.

11. Amisulpride.Pregnancy: dysmorphogenesis. Clozapine) 16. anti-cholinergics and quinidine. ANS: Orthostatic hypotention.  Tachycardia with risk of arrhythmia (least with aripiprazole). Risperidone. 8.Corneal and lens toxicity: Thioridazine-retinal deposit resembling retinitis pigmentosa. 9. 13. menstrual disturbance. Impotence (common with typical antipsychotics. Common with first generation anti-psychotics. 10. α- adrenergic blocking agents. Anti-muscarinic effects  Blurring of vision. 12. Risperidone.Seizure-decrease in seizure threshold.Cardiotoxicity (thioridazine. dryness of mouth (except clozapine which causes hypersalivation. Effects on tubero-infundibular pathways.Cholestatic jaundice 14.Weight gain (less with Haloperidol. olanzapine. Galactorrhoea. Aripiprazole. Clozapine. Loxapine). Pimozide.Hyperglycemia: highest risk with Clozapine. infertility. gynaecomastia. Quetiapine. Hyper-prolactinemia (absent with aripiprazole and less with olanzapine.  Urinary retention  Constipation  Increase in intra-ocular pressure. Risperidone. Quetiapine) Failure to ejaculate. Quetiapine).Blood dyscrasia (clozapine-agranulocytosis) 15. Risperidone. Drug interactions Important drug interaction occurs when they are combined with sedatives.can be controlled by giving Hyoscine butyl bromide). ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. Photoxicity. First generation anti-psychotics. Olazapine. 17. 7. 12 . urticarial reaction. IBRAHIM 6. clozapine.

9. Severe CNS depression 7.Angle closure glaucoma 11.Phaeochromocytoma 13. IBRAHIM Contra-indications 1. US:Mc Graw Hill.G. Quetiapine.S.. Basic and clinical pharmacology.T. BERTRAM. 5. 3. References 1..2010. 4.Myasthenia gravis with CYP 450 inhibitors. agranulocytosis: clozapine is contra-indicated. Essential of therapeutics. Principle of internal medicine.BPH 12. Risperidone. HARRISON. Comatoes state 6. GOODMAN & GILMAN’S. ROYAL PHARMACEUTICAL SOCIETY. Severe renal and hepatic disorders. Neutropenia. 12th ed. 3rd ed 13 . The pharmacological basis of therapeutics. olanzapine. 2012. US: Mc Graw Hill. 4. 12th ed. DM (especially second generation drugs such as Clozapine. J. 2014. SUSAN. ANTI-PSYCHOTICS LECTURE APRIL 2014 DR T. US: Mc Graw Hill. & ANTHONY. Patient with history of QT prolongation or severe cardiac disorders such as myocarditis. 2. 3. 2.B.. 18 th ed. 2013. London: BNF publication. Kaplan text book of psychiatry 6. BNF. SHUKLA.. cardiac failure. Parkinson’s disease 10.K. J.. Prolactin dependent tumours 8.2011. Uncontrolled epilepsy 5.