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Drugs Used in Psychiatry

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Drugs Used in Psychiatry Dr Noel Kennedy Clinical Lecturer and Consultant Psychiatrist Schizophrenia Positive symptoms - delusions ... – PowerPoint PPT presentation

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Title: Drugs Used in Psychiatry


1
Drugs Used in Psychiatry
  • Dr Noel Kennedy Clinical
    Lecturer and Consultant Psychiatrist

2
Schizophrenia
  • Positive symptoms
  • - delusions
  • - hallucinations
  • Negative symptoms
  • - apathy
  • - avolition

3
Schizophrenia Diagnosis (Schneider, 1959)
  • Hallucinations
  • - third person
  • - running commentary
  • - thought echo
  • Thought interference or Somatic passivity
  • Delusional perception
  • (also bizarre delusions DSM-IV, one month
    duration0

4
Schizophrenia - Epidemiology
  • 1 prevalence, higher cities, ethnic minorities
  • MgtF, late teens to early 20s
  • Two peaks in onset
  • - early onset, male, developmental delay,
    drugs
  • - late mid-life, female, preserved
    personality
  • Interst in substance abuse, prenatal viral
    exposure
  • Poor outcome - gt80 relapse, majortiy impaired

5
Schizophrenia Aetiology
  • Genetic
  • - First degree relative 10
  • - Twin studies MZDZ 484, Adoption studies
  • Neurochemical
  • - D2 blockade (amphetamines, animal models,
    receptor occupancy)
  • - Serotonin blockade (?5HT2 block, LSD,.5HT
    impact on dopamine )
  • - Glutamate (NMDA antagonists e.g.
    ketamine)

6
Antipsychotics- Classification
7
Typical antipsychotics D2 Antagonism
Mesolimbic (Antipsychotic)
HPA (? PRL)
Basal Ganglia (EPSE, Parkinsonism)
8
Typical Antipsychotics
  • High potency Clean (Likely EPSE)
  • - Butyrophenones (e.g. haloperidol)
  • - Piperazine (e.g. trifluoperazine)
  • Low potency Dirty (anticholinergic,
    antiadrenergic)
  • - Aliphatic (e.g. chlorpromazine)
  • - Thioxanthene (Zuclopenthixol)

9
Extrapyramidal Side Effects
  • Acute Dystonia (Young men, early, first episode)
  • Parkinsonism (cog-wheeling, rigidity,
    bradykinesia)
  • Akathesia (uncontrollable restlessness, suicide
    risk)
  • Tardive Dyskinesia (long-term tx, female,
    elderly)
  • Neuroleptic Malignant Syndrome

10
Neuroleptic Malignant Syndrome (NMS)
  • Early in tx (lt4 weeks) MgtF, 20
    mortality,mid-life
  • Clinical
  • - muscle rigidity
  • - pyrexia
  • - delirium
  • - pyrexia
  • - ??CPK, ?K ?Neutorophils, Myoglobinurea
  • Treatment
  • - respiratory support
  • - bromocriptine/dantrolene

11
Antipsychotics Other Side Effects
  • Anticholinergic (low potency)
  • - blurred vision, constipation, confusion, wt
    gain
  • Antiadrenergic (low potency)
  • - postural hypotension, sexual
  • ? Seizure threshold
  • Weight gain (low potency, clozapine, olanzapine)
  • Neutropenia/Agranulocytosis (clozapine)
  • Diabetes/Impaired GTT (clozapine, olanzapine)
  • Cholestatic jaundice (chlorpromazine)
  • ECG change, QT prolongation (low effect)

12
Atypical Antipsychotics
  • Definitions
  • - Less EPSE
  • - Mesolimbic specific or 5HT2/D2 antagonism
  • Clinical Potency
  • - As effective as typicals in positive
    symptoms
  • - Some more effective (clozapinegtolanzapine/
    sulpiridegtrest Davis et al.)
  • - May have more effect on negative symptoms

13
Atypical Antipsychotics
  • Sulpiride/Amisulpiride
  • - D2 blockade mesolimbic specific, ?PRL
    antidepressant
  • Risperidone
  • - 5HT2/D2 blockade, EPSE high doses, little
    sedation, wt gain
  • Olanzapine
  • - 5HT2/D2 blockade, significant weight gain
    (9), sedation
  • Quetiapine
  • - D2/5HT2/ blockade, sedative, few other
    s/e, ?potency
  • Clozapine
  • - treatment resistant scz, multiple
    receptors, agranulocytosis

14
Clozapine
  • Most effective treatment for treatment resistant
    schizophrenia (30 6 weeks, 70 1 year kane et
    al, 1988)
  • Multiple receptor occupancy
  • (D1, D2, D4, D5, 5HT2, 5HT3, adrenergic,
    muscarinic)
  • Many side effects including agranulocytosis
    (2-3)
  • May lead to reduction in suicide

15
Clozapine Important Side Effects
  • Neutropenia
  • - Weekly blood monitoring (18 weeks), 2-4
    weeks afterwards
  • Seizures
  • - Mainly myoclonic, dose related, valproate
  • Myocarditis/Cardiomyopathy
  • - 1 in 10,000-20,000
  • Pulmonary embolism
  • - 1 in 5,000, effect on antiphospholipid
    antibodies
  • Diabetes and weight gain
  • - 1/3rd within 5 years of treatment

16
Clozapine Other Side Effects
  • Sedation (early)
  • Hypersalivation (hyoscine)
  • Hypertension/hypotension
  • Tachycardia (early)
  • Constipation
  • Fever

17
Antipsychotics and Diabetes
  • Especially clozapine and olanzapine (30-40
    diabetes long-term)
  • Usually early in treatment
  • Needs regular monitoring
  • (Baseline HBA1C, OGTT, then 3-6 monthly)

18
Depression Treatment Symptoms
  • At least two of (gt2 weeks)
  • - persistent low mood (DMV)
  • - anhedonia
  • - poor energy
  • At least two of
  • - sleep disturbance
  • - appetite disturbance/weight loss
  • - impaired libido
  • - guilt cognitions
  • - poor concentration
  • - futility feelings/suicidal ideation
  • - social withdrawal

19
Depression - Epidemiology
  • 6-9 prevalence, higher women (FM 21)
  • Late 20s throughout life
  • Higher rates cities, low social class
  • Poor outcome high levels of disability
  • - 10 chronicity
  • - 10 unnatural death
  • - 70 long-term recurence
  • - 50 of time symptomatic over 10 years

20
Depression and subsyndromal symptoms over 10-year
follow-up (Kennedy et al, 2004)
21
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22
Theories of Depression
  • Monoamine Theory
  • - Deficits of monamines 5HT/Nad
  • - Most antidepressants increase monoamines
  • Neuroendocrine (HPA axis)
  • - Hypercortisolaemia/loss of circadian
    rthymn
  • - Failure of DST (60)
  • - Failure to supress CRH

23
Antidepressants Classes
  • Monoamine oxidase inhibitors (MAOI)
    - ?stores Nad/5HT by
    inhibiting MAO-A
  • Tricyclic antidepressants (TCA)
    inhibits 5HT/Nad neuronal
    reuptake
  • Selective serotonin reuptake inhibitor (SSRI)
    inhibits 5HT neuronal reuptake
  • Others
  • - venlafaxine - Nad/5HT reuptake/receptor
    inhibition
  • - mirtazepine - alpha 2, 5HT2 receptor
    inhibition
  • - reboxetine Nad reuptake inhibitor

24
Management of Depression General Principles
  • Antidepressants only effective (70)
  • Partial response a problem (40)
  • Length of treatment important (4-8 weeks)
  • Not all antidepressants are equal (meta-analysis)
  • Consider symptoms
  • Consider side efffects
  • Length of continuation/maintenance treatment

25
Consider Symptoms and Side Effects
NE
5HT
Mood Sleep Loss of pleasure
Attention Drive Appetite
Obsessions Anxiety Cognitions
26
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27
Selective Serotonin Reuptake Inhibitors (SSRI)
  • First line treatment
  • Effective in anxiety
  • Safe, flat dose response
  • - Escitalopram - ? More efffective than
    citalopram
  • - Fluoxetine long t1/2, potent inhibition
    CYP
  • - Paroxetine short t1/2, discontinuation
  • - Sertraline mild CYP inhibition

28
Selective Serotonin Reuptake Inhibitors (SSRI)
  • Common adverse effects
  • - nausea, vomiting, abdo pain, diarrhoea
  • - sweating
  • - headache
  • - agitation, insomnia, tremor
  • - hyponatraemia (SIADH) elderly, female,
  • - discontinuation syndrome (paroxetine)
  • - sexual dysfunction

29
Tricyclic Antidepressants (TCA)
  • Probably more effective than SSRI
  • S/E Anti chol, anti adren, anti hist action
  • Cardiotoxic OD, QT prolongation
  • Weight gain long-term
  • Doses prescribed too low
  • - Amitriptyline sedation, anti chol, ?BP
    postural
  • - Clomipramine similar s/e, 5HT anxiety/OCD
  • - Loferpramine less cardiotoxic, sedative
  • - Nortriptyline less s/e, elderly

30
Monoamine Oxidase Inhibitors (MAOI)
  • Mode of Action
  • - Block MAO A (Nad/5HT) and B (Dop/TYP)
  • - Avoid tyramine containing substances- ??BP
  • Clinical Potency
  • - Best for atypical or resistant depression
  • - Withdrawal 2 weeks, withdrawal effects,
    5HT syndroms
  • - Mocclobemide Reversible MAO A inh
  • - Phenelzine/tranylcypromine
    irreversible inh, non selective

31
Monoamine Oxidase Inhibitors (MAOI)
  • NB Lots of S/E MCQ answer yes
  • - anti cholinergic/anti adrenergic/anti
    histamine
  • - paraesthesia
  • - headache
  • - hepatotoxicity
  • - leucopenia
  • - hypertensive crises (9)
  • - sexual dysfunction

32
Other Antidepressants
  • Venlafaxine
  • - 5HT/Nad reuptake inhibitor like clomipramine
  • - meta-analysis higher proportion recovery
  • - linear dose response
  • - s/e discontinuation, short t1/2, BP, SSRI
    like
  • Mirtazepine
  • - ?2 antagonist, wt gain, sedation
  • Reboxetine
  • - selective Nad antagonist
  • Duloxetine
  • - 5ht/Nad reuptake inhibitor

33
Electroconvulsive Therapy
  • Most effective in TRD (80-85 response)
  • Well tolerated (6-12 treatments)
  • Best severe, agitated, elderly, depression
  • ?Nad/5HT transmission, Da, PRL oxyticin release,
    ?plasma cortisol, ?BBB permiability
  • Adverse effects
  • headache, muscle stiffness, memory, GA

34
Refractory Depression Definitions
  • Failure to respond fully to gt1 or several
    antidepressants (10-30)
  • Chronic duration lt2 years (10)
  • - least likely to be effectively treated
  • Partial response also a problem (gt40)

35
Management of TRD
  • Outrule medical cause/medications
    (e.g.
    diabetes, hypothyroidism, Cushings syndrome,
    dementia)
  • Investigate precipitants of depression
  • (e.g. bereavement, marital or family
    dysharmony, social factors)
  • Consider comorbidity or misdiagnosis
  • (e.g. anxiety disorders, substance abuse,
    dementia)

36
Management of TRD
  • Psychoeducational
  • - self-help books
  • Pharmacological
  • - optimise antidepressant treatment
  • - switch class of antidepressant
  • - augment antidepressant
  • Psychological
  • - CBT/interpersonal psychotherapy prevents
    early relapse
  • -

37
Management of TRD Augmentation
  • First low dose lithium

  • 50 response within 1 week
  • Second low dose atypical antipsychotics
  • Third Triiodothronine (T3), lamotrigine,
    tryptophan
  • Fourth Combine antidepressants

38
?
39
Anxiety Disorders
  • Types
  • - Generalized Anxiety Disorder
  • - Social phobia
  • - Agoraphobia
  • - Obsessive Compulsive Disorder
  • Treatment
  • - Exposure therapy
  • - SSRIs and Clomipramine, Benzos (lt2
    weeks)

40
Bipolar Affective Disorder - Epidemiology
  • 0.8 prevalence, women later onset (FM 1.21)
  • Onset early 20s, 50 mania,
  • Higher rates cities, ?higher social class
  • Strongly genetic (20 first degree relative)
  • Very high proportion recur (gt90)
  • Women more depression BPIIgtBPI

41
Management of BAD Acute
  • Treatment of mania
  • - Antipsychotics or benzodiazepines
  • - (semi)sodium valproate/lithium
  • Treatment of bipolar depression
  • - Lithium treatment of choice
  • - Lamotrigine
  • - Antidepressants risk of inducing
    mania/rapid cycling

42
Management of BAD Maintenance
  • Moderate dose lithium (0.8-1.2 meq/l)

  • (60-70), prevents mania and depression
  • ValproategtCambamazepine
  • Better for mania than depression
  • Lamotrigine
  • Better for depression than mania
  • Atypical antipsychotics recent data

43
Lithium
  • Acute and maintenance (depressiongtmania)
  • Mode of action
  • - salt, not metabolised, 2/3 excreted by 24
    hrs, Avoid NSAID ACE Inh
  • - G proteins, Na/K ATP ase, cAMP
  • Side effects
  • - Immediate dry or metallic taste,
    diarrhoea, tremor
  • - Nephrogenic diabetes insipitus
    polydipsia/polyurea (ADH resistance)
  • - Later Nephropathy (5), Hypothyroidism
    (3 pa), weight gain/oed
  • - Toxicity (.2.0 meq/l) coarse tremor,
    confusion, ataxia, coma

44
Other Mood Stabilizers
  • All are anticonvulsants and act on Na channels
    and GABA
  • Valproate
  • - Acute mania, maintenance, rapid cycling
  • - S/E sedation, weight gain, hair loss,
    hepatic failure, leucopenia, terato
  • thrombocytopaenia, highly plasma protein
    bound, displacement
  • Cambamezipine
  • - Acutr mania, rapid cycling, agression S/E
    leucopenia (10) agran, sed
  • apl anaemia, enzyme inducer OCP, rash
    Stevens-Johnson syndrome
  • - Lamotrigine
  • - Bipolar dsepression S/E rash, headache,
    nausea, ataxia
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