Dr Amaury Delgado-Hernandez ST5 General Adult Psychiatry

GENERAL PRINCIPLES IN PSYCHOPHARMACOLOGY

DR AMAURY DELGADO HERNANDEZ ST5 IN GENRAL ADULT PSYCHIATRY 3

• History and Mental State 12

• Descriptive Psychopathology 24

• Cognitive Assessment 10

• Neurological Examination 10

• Assessment 16

• Description and Measurement 6

• Diagnosis 12

• Classification 8

• Aetiology 12

• Prevention of Psychological Disorder6

• This breakdown is intended as a general guide to the content of Paper 1 and is subject to change

• Paper 1 pass rate for December 2011= 54.8%

• Basic Psychopharmacology14

• Human Psychological Development8

• Social Psychology4

• Basic Psychological Processes

14

• Dynamic Psychopathology 12

• Basic Psychological Treatments 8

• History of Psychiatry 8

• Basic Ethics and Philosophy of Psychiatry 8

• Stigma and Culture 8

PAPER 1 EXAM OF THE RCPSYCH

PROGRAMME

1. History of Psychopharmacology2. Classification3. Placebo Effect4. Drug Approval5. Ethnopharmacology6. Pharmacokinetics7. Pharmacodynamics8. Type of Adverse Reaction9. Mechanism of side effect

BRIEF HISTORY 1915 Macht and Mora coined the term psychopharmacology when studying opioids

1931 Sen & Bose (Plant Rauwolfia)=Reserpine.

1949 Cade in Australia discovered the use of Lithium compound in mania.

1950-1952 Delay and Deniker antipsychotic properties of Chlorpromazine

1952 Iproniazid anti-tuberculosis with antidepressant effect (mood lifting properties)

1954 First BZD Chlordiazepoxide in Austria Leo Sternbach

1955-1958 Klein TCA (Kuhn) and MAOIs.(Klein)

1958 Janssen synthesised butyrophenone (Haloperidol)

1963 Cheese reaction was proposed by Blackwell.

1970 Fluoxetine tested but not taken until 1987

CLASSIFICATION ACCORDING TO MOLECULES

• Aliphatic phenothiazines- Chlorpromazine, promazine, triflupromazine

• Piperidine derivatives- Thioridazine• Piperazine derivatives- Trifluoperazine,

Fluphenazine, prophenazine,• Butyrophenones– Haloperidol, Droperidol• Thioxanthenes- Thiothixene, Flupenthixol,

Zuclopenthixol• Dihydroindoles – molindone• Diphenylbutylpiperidine – pimozide (long t1/2)• Dibenzoxapine – loxapine• Benzisoxazole derivative- risperidone• Substituted benzamides- Amisulpride, Sulpiride• Dibenzodiazepine - Clozapine• Dibenzothiazepine - Quetiapine• Thienobenzodiazepine - Olanzapine• Benzisothiazole- Ziprasidone• Arylpiperidylindole (quinolone) Aripiprazole

CLASSIFICATION ACCORDING TO MOLECULE • Tertiary amines – imipramine, amitriptyline, clomipramine,

dothiepin, trimipramine (also venlafaxine)• Secondary amines – desipramine, amoxapine, nortriptyline

and protriptyline (also duloxetine) [more potent mg to mg basis; less sedating; more noradrenergic, less antihistaminic or anticholinergic than tertiary]

• Hydrazine derivatives - phenelzine, isocarboxazid (greater hepatotoxicity than tranylcypromine, non hydrazine compound)

• Aminoketone - Bupropion (amphetamine like)• Azaspironedecanedione Buspirone• Triazolopyridine - Trazodone, nefazodone.• Imidazopyridine - Zolpidem• Pyrazolopyrimidine - Zaleplon• Cyclopyrrolone - Zopiclone

CLASSIFICATION ACCORDING TO MA

• SSRIs citalopram, paroxetine, fluoxetine, sertraline and fluvoxamine (S enantiomer of citalopram ) -Escitalopram

• SNRIs – serotonin and noradrenaline reuptake inhibitor venlafaxine, milnacipran, duloxetine

• NARI – Noradrenaline reuptake inhibitor -reboxetine• NaSSA – Noradrenergic and specific serotonergic antagonist –

Mirtazepine and• mianserin• DARI – Dopamine reuptake inhibitor -Bupropion• RIMA – reversible inhibitor of Monoamine A oxidase -

moclobemide• SARI – serotonin antagonist and reuptake inhibitors –

nefazodone, trazodone.

PLACEBO• “Intervention deliberately used for non-specific psychophysiological

treatment effect”.• Placebo effect in research: Difference in outcome between placebo and

an untreated control group.• Nocebo: Placebo that produces significant SE.• Placebo sag: The fading of the response with chronic and repetitive

administration. • Best placebo response (pain and disorders of autonomic sensation

Nausea, Bronchial asthma)• Psychiatric illness (Placebo Response)• Depression 25-60%/ Mania 25% / Schizophrenia 25-50% / Panic

Disorders 70%• Placebo fails in degenerative and vascular conditions

DRUG APPROVALPreclinical-Animal studies

2 different animal species tested for Mutagenicity, carcinogenicity and organ toxicity

Human trials-Volunteer Phase 1safety

Small group of healthy volunteers and safety, tolerability and pharmacokinetics

Human Trials-Patients Phase 2effectiveness

Hundreds of patients with target disease vs placebo (RCT)

Human Trials Patients Phase 3 Superiority

Superiority or equivalence to standard looking at comparative efficacy and tolerance profile. In this phase the drug undergoes RCT with double-blinding. Looking at how well it works and side effects

Human Trail Post-marketing Surveillance phase 4

Drugs undergoes approval, monitoring continues and drug could be removed if abnormal findings