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Psychopharmacology

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Richard Duffy

on 2 April 2015

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Transcript of Psychopharmacology

Neurological symptoms (diplopia, blurred vision, fatigue, nausea, vertigo, nystagmus, ataxia)
Transient leukopenia in 2%
Transient thrombocytopenia
Rash in 10%
LTF elevation in 5-15%
Hyponatremia
Teratogenicity-NTD, fingernail hypoplasia, developmental delay

Psychopharmacology
Prof Brian Lawlor
Dr Richard Duffy

Mood Stabilizers
Anti-Psychotics
Others
BDZ/
Sleepers

Drugs used in dementia
Drugs used in Addiction
Treatments of Side effects
Drugs used in Child Psychiatry
Typical Antipsychotics
Atypical Antipsychotics
Lamotrigine
CBZ
Lithium
Sodium
Valproate

SSRIs
Anti-
Depressants

SNRIs
TCAs
MAOIs
Other
Fluoxetine (Prozac)
Citalapram (Cipromil)
Escitalopram (lexapro)
Fluvoxamine
Paroxetine - most S/e
Sertraline (Lustral)
Indications
Side Effects
Treatment of moderate to severe depression
GAD
Panic disorder
Social Anxiety disorder
OCD
Bulimia (fluoxetine)
PTSD (Sertraline)
HypoNa
Mania/hypomania
Bleeding -consider other meds
Sexual dysfunction
GI upset
Headache
Suicidal ideation in young males NNH-143, NNT-10 (fluoxetine and citalopram)
Seizures
Serotonin syndrome
General
Takes 3-6/52 to work
Lower dose for anxiety
Higher dose in eating disorders/ OCD
MOst commonly prescribed ADT
Inhibit CYP2D
Duloxetine (Cymbalta)
Venlafaxine (Effexor) - SSRI at low dose
Indications
Unipolar depression
GAD
Social anxiety
Panic disorder
Duloxetine - IBS
Side Effects
More S/e than SSRIs
GI Upset
Mania/hypomania
Acute angle glacoma
Akathisia
Palpitations
Tremor
Erectile dysfunction
Raised BP at higher doses
Amitriptyline (TA)
Clomipramine (TA)
Trimipramine (TA)
Dothiepin (TA)
Imipramine (TA)
Desipramine (SA)
Nortriptyline (SA)
Lofepramine (SG)
Isocarboxazid
Phenelzine
Tranylcypromine
Moclobemide
Agomelatine
Depot Antipsychotics
Amisulpride
Aripiprazole
Clozapine
Olanzepine
Paliperidone
Quetiapine
Risperidone
Ziprasidone
Asenapine
Chlorpromazine
Flupentixol
Haloperidol
Trifluperazine
Sulpride
Zuclopenthixol
Perphenazine
Flupentixol
Haloperidol
Zuclopenthixol
Risperidone
Olanzepine
Paliperidone
Zopiclone
Zolpidem
Diazepam
Alprazolam
Chlordiazepoxide
Flumazepine
Temazepam (Short T1/2)
Lorazepam (Short T1/2)
Donepezil (reversible AChE-I)
Rivastigmine (Irreversible AChE-I)
Galantamine (reversible AChE-I)
Memantine (NMDA antagonist)
Methadone
Naloxone
Naltrexone
Acamprosate
Buproprion
Disulphram
Thiamine
Chlordiazepoxide
Side Effects
Tranylcypromine-tyramine free diet required
- Cheese effect
- Serotonin syndrome
S/E
>1/10
Diarrhoea
Nausea
Headache
Dizziness
Vomiting
>1/100
hallucinations
Depression
Muscle cramps
Rash
Fatigue
Issues
Tolerance
Abuse
Dependence
W/D
Variable T1/2 (up to 100hrs)
Disinhibition (10 -58 (EUPD) %
Liver Metabolised besides Lorazepam
Falls (Hip fracture RR 1.5)
More sleep but reduced REM
Indications
Certain forms of epilepsy
Severe muscle spasm
Rapid Tranquillisation (Agitation in mania, dementia, depression)
Short term anxiolytic
Short term hypnotic
DTs
BDZ w/d
S/E
Sedation
EPSE
Anti Cholinergic
Hypotension
Prolactin elevation
Diabeties
Weight gain
Seizures
Weight gain
Metabolic syndrome (Ix: 3,6,12/12)
OTc abnornalities >500 risk of T de P
Increased Mortality in dementia
CVAE in dementia (x2-3)
Postural Hypotension
Prolactin elevation
Sedation
EPSE
Anti Cholinergic
NMS
Clozapine
S/E
Sedation
Wt gain
Metabolic syndrome
Poor glycaemic control
Neotropenia (1-2%)
Pancytopenia
DVT/PE
Cardiomyopathy
Hypersalivation
Seizure
Hypotension
Monitoring
Neutrophils, platelets, monocytes
Weekly for 18 weeks
Bi-weekly till 1 yr
Then monthly
Also check - weight, BP, BM, Lipids
DO NOT STOP CLOZAPINE FOR A PRE OP PATIENT

DO NOT STOP WITH OUT REASON
Considerations
Non intentional non adherence
Detained patients (long term)
Infection at site and nerve damage
Test dose
Not for anti psychotic naive
Procyclidine - Anti- cholernergic for dystonia
Hyoscine bromide (kwells) - For hypersalivation
S/E
TERATOGENICITY (4-12% 1st Trimester)
Polyuria (36%)
Polydipsia (30%)
Thyroid dysfunction (hypothyrois 4-10% raised TSH 30%) F>M
HyperPTH
Hair loss
Worsening of skin conditions
Metalic taste
Tremor (4%)
Mild cognitive decline
Weight gain (19%)
Tiredness (12%)
Diarrhoea (9%)
ECG changes - bradycardia, ST and T wave changes, T wave depression
Monitoring
Monitor U/e, TFT and Li level
Li level 0.4 - 1.2 greater than 0.8 in BPAD
At 1.5 becomes toxic
Weekly tests till therapeutic range reached
Li levels every 3/12
TFT and U/e as indicated or every 6/12
Blood levels only valid if 10-14hrs post dose
Interactions
Toxicity
>1.5 GI symptoms (anorexia nausea and diarrhoea) and neuro symptoms (weakness, drowsiness, ataxia, coarse tremor, muscle twitching)
>2 disorintation, seizures progressing to coma and death
>3 use peritoneal or haemodialysis
General
Acts on GABA complex not fully understood mechanism
Highly protein bound
Hepatically metabolised
Discontinue slowly
Once stabilised, can be given as single dose
Titrate to 50-150 mcg/mL
Indications
Side effects
Treatment of Mania first line (Comparable to Li++, haloperidol)
53% show moderate or marked reduction in symptoms
Response several days to 2 weeks
In combination with an anti depressant for BPAD Depression
Prophylaxis in BPAD
Not first line in women of child bearing age
Best Tolerated anticonvulsant
Nausea
Lethergy, confusion
Wt. gain - pre treatment BMI
Tremor (25%)- some alos develop parkinsonism and cognitive decline which is reversible
Teratogen - if needed prophylactic folate
Very rarely fulminant hepatic failure - monitor LFTs and if abnormal coag
Sedation
Asprin can cause toxicity as highly protein bound
Warfarin is less strongly bound hence can cause bleeding
Indications
Grand Mal and focal seizures
Trigeminal neuralgia
BPAD not responsive to Lithium (3rd line prophylactic agent 30-60% have significant benefit)
Not first line for mania
Side effects
Sedation
Sexual S/e
Postural hypotension -α-lytic effects
Tachycardia
Arrhythmia - conduction block - Increase PR interval (1/52 supply can be fatal
Confusion
Seizures (0.1-4% on all ADTs TCA>SSRI>MAOI)
Trazadone
Reboxetine
Mirtazepine
Melatonergic agonist increases dopamine in the frontal lobe
5-HT 2C antagonism
Limited sexual dsyfuncion
Can cause raised LFTs >x3 stop
Monitor at 3,6,12,24 weeks
Enhances quality of sleep with out being sedating
alpha 2 antagonist
Anti histamine
Can cause weight gain and blood dyscrasias
Good Sexual functioning profile
NA reuptake inhibitor
Sympathetic S/e
least hypo Na
Questionable effectiveness
Seretonin antagonist and reuptake inhibitor
Sedation
Not anticholinergic and less cardiotoxic
ACE Inhibitors
Angiotension II receptor antagonists
Diuretics
NSAID (Decrease Li)
Carbamazepine
SSRIs
Caffeine (stopping can increase Li)
Decreased thirst
Dehydration
Increased Na reabsorption
Increased Li levels
Espically thiazide diuretics
Loop can be perscribed
Improved metabolic profile
Only licensed in BPAD
Less wight gain >1kg / yr
Tetracyclic antipsychotic
Treats affective symptoms

Decision making in prescribing
Rational vs Emotive thinking
Evidence base
Level of evidence 1++ to 4
Grade of A to D
You are asked to review a 40 year old man with schizophrenia who has relapsed on olanzapine 20mg. His BMI is 29

Your approach would be:

1. Increase olanzapine
2. Switch to haloperidol
3. Switch to weight neutral atypical
4. Trial of clozapine

Lawlor 08/14

A 19 year old female presents to your surgery with a 4 month history of amenorrhea. She has a history of Bipolar disorder and is taking risperidone 2 mg/day and lithium 800mg/day. She is worried about the fact that she has missed her period.

What’s likely to be causing her amenorrhea?
What are the important issues for discussion?

A 45 year old man is admitted with a 2 week history of overspending, lack of sleep, increased energy, irritability and inability to concentrate and work. He has a history of depression over the past 5 years.

What is the likely diagnosis?
What is the appropriate drug treatment?

A 50 year old man presents to your surgery with a 2 year history of short term memory loss. He is unable to remember messages and keeps asking the same questions. He has had to quit his job as a civil servant because of his forgetfulness.

What’s the likely diagnosis?
What investigations are indicated?
What treatments, if any, are available?

A 78 year old man has become very agitated following a left sided THR. He had been operated on as an emergency following a hip fracture after a fall at home. He has a background of cardiac failure, COAD, osteoporosis. His wife says that his memory was fine before the operation although he was a little forgetful. He is disoriented in time and place and sees robbers coming onto the ward at night. He is fearful for his life and believes that the nursing staff are conspiring to have him assassinated. He has tried to pull out his IV cannula on a number of occasions and is striking out at nursing staff

What is the diagnosis?
Is medication is indicated?

You are asked to see a 75 year old man in the ED with a background of cognitive impairment sent in by his GP with increasing paranoid beliefs regarding being robbed and becoming aggressive to his carers. He claims that there are people breaking into his house and rifling through his belongings. You advise:

You are called to the ED to assess a 22 year old male with severe agitation, aggression. He was brought in by the guard because he appeared to believe that the IRA was chasing him and his life is under threat. He doesn’t feel safe and has assaulted the Gardai believing that they agents of the IRA. The best course of action is:

After 3 weeks there is no significant improvement on venlafaxine XL 225 mg and risperidone 2mg. What are the pros and cons of the below interventions?

Lawlor 08/14

You are asked to see a 21 year old woman in A&E with acute onset of severe breathlessness and chest tightness at a 21st party. A doctor who was attending the party sent her to A&E to rule out a cardiac cause for her chest tightness and shortness of breath.

What further information do you require?
What’s the likely diagnosis?
What drug treatment, if any would you offer this young woman?

Side effects
70-80% protein bound
Induces its own metabolism
Therapeutic range 4-15mmol/L-neurological side effects more common >9 mmoles/L
Mechanism of action
Inactivates voltage sensitive Na+ channels decreases Na+ influx-
Affects multiple neurotransmitter
Unknown
Lawlor 08/14

Lawlor 08/14

Lawlor 08/14

Slowing of central information processing
Protein kinase C which has been implicated in long-term potentiation in hippocampus

Lawlor 08/14

Age
Renal disease
Organic brain disease
Physical illness- vomiting diarrhea
Low Na intake or high Na excretion
Pregnancy
Genetics

Risks for S/E
Lawlor 08/14

Narrow therapeutic index
35-93% of patients have S/e
Non-compliance especially due to cognitive dysfunction
Side effects are dose related

77% of lithium treated schizoaffective disorder patients improve
Anti-aggressive effects
Lithium and other disorders

34% relapse on Li, 81% relapse on placebo
50% relapse within 5/12 of abrupt termination
Relapse is reduced if tapered slowly
50% of BPAD patients have an inadequate response to Li++ alone
Rapid cyclers or mixed states show a poorer response
Personality disorder and substance abuse associated with poorer response

Prophylaxis of bipolar disorder
Lithium (at therapeutic doses x10-14 days)
T3
L-tryptophan augmentation of MAOIs -historical
Combination of SSRI, Bupropion or SNRI with Mirtazapine
Combination of ADTs and atypical antipsychotics

Augmentation strategies

1/3 of responders did so after 6/52
1/2 of remitters did so after 6/52
Modest improvement at 6/52
Dose increase
Further exposure (up to 10 weeks)
Switch in or out of class - moth effective
Remission chance reduces with each switch
STAR*D trial
Postural hypotension
Insomnia
Sexual side effects
70% response rate in MDD
Lag to onset of action of 10 days to 3 weeks
Biological symptoms predict better response
Dysthymia can respond to ADTs

A 37 year old woman who is 3 months post partum presents to your surgery with a 3 week history of poor sleep, loss of appetite and interest and feelings of inability to cope. She cries all the time in your office and feels she can’t go on.

What’s the likely diagnosis?
What are the important issues?
What is your approach to treatment?

Effective in moderate-to severe Alzheimer’s disease when ACHEI are not tolerated or ineffective
Modest effect on cognition and function
Side effect profile similar to placebo
Indicated for mild to severe disease (MMSE 10-24)
Modest improvement in cognition in 30-40%
Can improve function and behaviour
Symptomatic and not disease modifying
56 month delay in decline
Effect on QoL less certain
NNT 5-15
Can combine with Memantine


1% of all exposed to (typical) neuroleptics
Typicals>>atypicals
Mortality 20%
Clozapine is lowest risk
D1, D4, 5HT2 blocker,
Weak D2 blocker in nigrostriatal system
Anticholinergic,
Gynecomastia
Galactorrhea
Impotence
Infertility
Amenorrhea
Osteoporosis

Overall prevalence of 15-20%
40-50% Reversible
Risk Factors
Age
Organic brain disease
Affective disorder
30% per year in > 65’s on typical agents
<5% per year in >65’s on atypicals

2Non-commercial trials comparing typicals and atypicals chronic SCZ
Newer drugs - no more effective or better tolerated
Conclusions: Careful prescribing of typicals may be a useful option
CUtLASS & CATIE

You are asked to see a 60 year old man on the AMAU who was brought in with collapse 2 days ago. He has begun to behave very erratically, threatening staff and they feel he should be discharged. You complete an assessment and find that he is confused, has a tachycardia and is tremulous. You feel that he is likely in the DTs. You advise:

The collateral indicates an abrupt onset over the past 4 days and there are prominent visual hallucinations of people coming into the house. He appears to have an E Coli UTI. You recommend the following:

At 9 months, the lithium and risperidone have been successfully tapered and discontinued. She comes back to see you and says that her sleep has dis-improved but despite this her energy levels are excellent. Her husband feels that she is somewhat overactive and asks is the medication too strong for her.
What’s possibly happening here?


After 6 weeks treatment with VXL 300mg, lithium 800mg, risperidone 2mg, she appears to be beginning to respond in terms of her mood, but her husband contacts you to say that her sleep is now much worse, she’s agitated and somewhat confused and complaining of palpitations. He wonders if it’s a side effect of the medications. The most likely diagnosis is:

Lawlor 08/14

39 year old female with a 4 week history of low mood, loss of pleasure, middle insomnia and poor appetite with a passive death wish. She believes she has no future and that she will lose her job because of her condition. Her mother died 2 months ago. There is a family history of ‘mood issues’. She drinks socially at week-ends only.
What is the differential diagnosis?
What are the treatment options?
Is there a role for "Z-drugs"?
When will you see her back?
Lawlor 08/14

Try to minimise psychotropic medication in first 12/52
Risk/Benefit analysis
Untreated psychosis or affective illness often higher risk then medication
All psychotropics cross placenta and excreted in breast milk (only important BDZ, Li and anticonvulsants
Lithium (Epstein’s anomaly)
Carbamazepine and sodium valproate
Foetal Valproate Syndrome
Neural tube defects X10
Distinct facial phenotype
BDZ - teratoenic facial malformations

1.5% of population use BDZs for > 1 year
1.5:1 females: males
44% have GAD
27% have personality disorder
17% have major affective disorder

Inhibits stimulated pre-synaptic release of glutamate
Efficacy in bipolar dession
Effective in rapid cycling BPAD
Skin rash can be problematic

Lawlor 08/14

Lawlor 08/14

Lawlor 08/14

Cluster headache
Preliminary use in HIV treated patients with zidovudine (Li++ stimulated leukocytosis)
Antiviral effects against HSV
Non-psychiatric uses of Lithium

Useful in bipolar depression but takes 3-4/52
79% of bipolar patients respond compared to 36% of unipolar patients
50% of treatment refractory patients respond to Li augmentation

Lithium and depression
Prevents recurrence of affective episodes in BPAD
Acute anti-manic effects (70-80% effective)
Lag phase of 5-7 days
Antidepressant effects
Prevention of recurrence of unipolar depression
Mechanism of action
Mood stabiliser
If severe add ADTs
Avoid TCA
Taper after 2-6/12 following remission
Quetiapine monotherapy
Treatment of bipolar depression

Medication not 1st line in mild depression
Monotherapy for 4-6 weeks
SSRIs are considered 1st line
Adequate trial at adequate dose
Then switch class or augment
Then consider ECT
Care when switching agent--may need wash out period
Treat 6-9 months for single episode
18-24 months for recurrent episode
? long-term prophylaxis for >3 episodes or >75 years

Treatment of unipolar depression

Discontinue neuroleptics
Supportive measures
Dopamine agonists
Dantrolene
ECT
10% risk of recurrence on re-exposure
Dystonic reactions within hours to days (2-20% Torticollis, tongue, occulogyric crisis.
Akathisia within 1-2 weeks (50-60%)
Parkinsonism from 1-6 weeks (40-50% - warning in DLB
Tardive dyskinesia from 6 months-2 years
TCAs/SSRIs/SNRIs
Pregabalin
MAOIs
Trazodone
Buspirone


Alternatives?
Lawlor 08/14

Lawlor 08/14

Rapid and complete, peak
Effects at 1-4 hours
Food and antacids delay
Cross BBB by diffusion
Brain concentration correlates
with unbound plasma fraction
Long T1/2 and active metabolites
Mechanism
Contraindications
Sleep apnea
Moderate to severe COPD
Substance misuse

Lag phase of 5-7days
75% show moderate improvement
50% relapse rate over 2 years vs. 85% on placebo

Older age
Female gender
Previous history
Diuretics
(dopamine reuptake blocker)-licensed for smoking cessation but an effective antidepressant
Bupropion
General
Block 5HT and NA reuptake
Dose needs to be titrated non linear
Lofepramine safer in overdose
Sympathetic S/e - Muscarinic blockade
dry mouth
blurred vision
constipation
urinary retention
Needed for the non-selective irreversible medication - Phenelzine
Other S/E
Case Study
General
Indications
Better response in
Rapid cycling, dysphoric or mixed mania
Older age at onset
Associated with medical or neurological illness
Lower incidence of familial BPAD
General
Potentiates GABA at GABA A receptors
Cerebellum-ataxia
Brain stem or cortex-sedation hypothalamus-neuroendocrine;
Hippocampus-amnesia
Limbic system-anti-anxiety/anti-conflict

AChE-I
General
Greatest risk for
Typicals
Risperidone
Supiride
Amisupiride
High fever
Autonomic instability
Rigidity
Altered consciousness
Raised CPK, WCC

Treatments
Symptoms
General
SCZ Tx
Pregnancy
Mechanism
Case Study
Case Study
Case Study
Case Study
Case Study
Case Study
Case Study
Case Study
Case Study
Full transcript