1. Revision of previous lecture Depression Not only psychiatrics prescribe antidepressant drugs… oncologist, pediatric SSRI=specific=less side effects=reduction in sexual ability Always describe drug according to the side effect not the efficacy SNRI= main side effect is hypertension After 8 weeks of Tx of 100 pt= only 50 will respond to the Tx=only 20 of those have remission+ only 20 of those have reduction in symptoms Most serious problem in depressant pt is suicide

2. Schizophrenia Pathogenesis is unknown. Onset of schizophrenia is in the late teens - early ‘20s. Genetic predisposition -- Familial incidence. Multiple genes are involved. Afflicts 1% of the population worldwide. A thought disorder

3. Schizophrenia Mainly In males esp. in second decade. smoking is a risk factor. Increase dopamine In CNS. القدرة الادراكية تقل... القدرة على التكلم وعمل علاقات اجتماعية بتقل Positive Symptoms. Hallucinations, delusions, paranoia, ideas of reference. Negative Symptoms. (some say bcz of decrease dopamine in some parts in the brain or increase serotonin!!!) Apathy, social withdrawal, anhedonia, emotional blunting, cognitive deficits, lack of motivation to interact with the environment. These symptoms are progressive and non-responsive to medication. Pt may cure in his own…with cognitive Tx Placebo is very effective as antipsychotic and anti depressant (35%).

4. Schizophrenia Drugs currently used in the prevention of psychosis. ** These drugs are not a cure ** Schizophrenics must be treated with medications indefinitely, in as much as the disease in lifelong and it is preferable to prevent the psychotic episodes than to treat them. SCHIZOPHRENIA IS FOR LIFE There is no remission

5. Dopamine Theory of Schizophrenia Many lines of evidence point to the aberrant increased activity of the dopaminergic system as being critical in the symptomatology of schizophrenia. There is a greater occupancy of D2 receptors by dopamine => greater dopaminergic stimulation Effect of drug appears after 9 weeks All antipsychotic drugs should be taken before sleep bcz of sedative effect

8. Classification of Antipsychotic drugs Main categories are: – Typical antipsychotics :dopamine antagonists( induce extrapyrimidal side effect (Tardive dyskinesia: irreversible) and Parkinson) Phenothiazines (chlorpromazine, perphenazine, fluphenazine, thioridazine et al) Thioxanthenes (flupenthixol, clopenthixol) Butyrophenones (haloperidol, droperidol) – Atypical antipsychotics: serotonin antagonists – (e.g. clozapine, risperidone>>> أكثر انتشارا في الأردن غالي الثمن ), sulpiride, olanzapine)

9. Classification of Antipsychotic drugs Distinction between ‘typical’ and ‘atypical’ groups is not clearly defined, but rests on: – Incidence of extrapyramidal side-effects (less in ‘atypical’ group) – Efficacy in treatment-resistant group of patients – Efficacy against negative symptoms.

10. 10 First Generation Antipsychotic Drugs Compound Seda- tion Hypo- tension Motor (EP) Effects Phenothiazines Chlorpromazine:حفظ Fluphenazine Haloperidol: most effective حفظ +++++ ++ ++++ ++

11. 11 Second Generation Antipsychotic Drugs Compound Sedation Hypo- tension Motor effects ++ +++ +/++ Dose dependent Clozapine مهم Clozaril ++ - Risperidone: maximum dose:6mg مهم جدا 0/+ Aripiprazole Abilify Risperdal

12. 12 Pharmacological effects of antipsychotic drugs: blockade of DA action

13. 13 Tolerance and dependence to antipsychotic drugs Not addicting Relapse in psychosis if discontinued abruptly Tolerance develops to sedative effects No tolerance to prolactin secretion No tolerance to antipsychotic effect

14. Withdrawal-like syndrome 1.Symptoms: nausea, vomiting, insomnia, and headache 2.Symptoms may persist for up to 2 weeks. 3.Symptoms can be minimized with a tapered reduction of drug dosage.

15. 15

16. 16 Aripiprazole Partial agonist at D2 receptor Intrinsic activity depends on synaptic levels of DA Affinity for muscarinic, α 1 -adrenergic, serotonin and histamine receptors Good oral absorption, 3-5 hr to peak plasma concentration, long elimination half life Few extrapyramidal side effects Efficacy is less than others Little hypotension

17. Tardive dyskinesia comprises mainly involuntary movements of face and tongue, but also of trunk and limbs, appearing after months or years of antipsychotic treatment due to accumulation of the drug. Irreversible side effect You should follow your pt over years of the Tx

18. Risperidone Endocrine effect  One of the most prescribed drugs in Jordan.  In women, these disturbances include:  galactorrhea  loss of libido  delayed ovulation and menstruation or amenorrhea.  In men, these disturbances include:  gynecomastia  impotence.  Ultra-rapid metabolizes (13% of the Jordanians) need higher dose Patients on antipsychotic drugs have low cognitive and complex motor abilities. In psychiatry, we start the drug on high dose to relieve the primary symptom, then reduce the dose.