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
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
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%).
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
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
Classification of Antipsychotic drugs • Main categories are: • Typical antipsychotics :dopamine antagonists( induce extrapyrimidal side effect (Tardivedyskinesia: 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)
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.
First Generation Antipsychotic Drugs Motor (EP) Effects Seda-tion Hypo-tension Compound Phenothiazines +++ ++ ++ Chlorpromazine:حفظ Fluphenazine + + ++++ Haloperidol: most effective حفظ + + ++++
Second Generation Antipsychotic Drugs Motor effects Hypo-tension Compound Sedation Risperidone:maximum dose:6mg مهم جدا +/++ Dose dependent +++ ++ Risperdal Clozapine مهم Clozaril ++ - ++ Aripiprazole Abilify 0/+ 0/+ 0/+
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
Withdrawal-like syndrome • Symptoms: nausea, vomiting, insomnia, and headache • Symptoms may persist for up to 2 weeks. • Symptoms can be minimized with a tapered reduction of drug dosage.
Aripiprazole • Partial agonist at D2 receptor • Intrinsic activity depends on synaptic levels of DA • Affinity for muscarinic, α1-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
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
RisperidoneEndocrine 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 onantipsychotic 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.