Transcript Dogsbody - Monash University

Antidepressants
Sue Henderson
Clinical Indications
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Mood disorders
•
Anxiety disorders
•
Eating disorders
•
Chronic pain
•
Incontinence
Personal perspective
• “I don’t take Prozac for fun. And it has not
changed my personality. I am not
ridiculously happy but I do not spend
most days miserable about being here,
there or anywhere and no longer have a
need to vomit before I have to talk to a
work related colleague or deal with
anything slightly stressful.” (Dietz, 2000,
p. 37)
Use of antidepressants in the
Australian population, 1975–
2002
(Mant et al., 2004)
Classes of antidepressant as
proportion of total sales of
antidepressants in the Australian
population, 1990–2002
(Mant et al., 2004)
Utilisation of top-selling*
antidepressants in the Australian
population, 1990–2002
(Mant et al., 2004)
Major and sub-classes
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Based on 3 physiological actions:
1. Reuptake inhibition
2. Enzyme inhibition
3. Receptor blockade
(Nash & Nutt, 2007).
Reuptake inhibitors
• Selective Serotonin Reuptake
Inhibitors( SSRI)
• Tricyclic Antidepressants (TCAs)
• Selective Serotonin and NorAdrenaline Reuptake Inhibitors
(SNRI)
• Nor-adrenaline Reuptake Inhibitor
(NARI)
Enzyme inhibitors
• The following antidepressant
subclasses work by inhibiting the
action of enzymes:
• Reversible Inhibitors of Mono-Amine
Oxidase type A (RIMA)
• Mono-Amine Oxidase Inhibitors
(MAOI)
Receptor blockers
• Nor-adrenergic and Specific
Serotonin Antidepressants (NaSSA)
work by blocking receptors.
Therapeutic effect
• Time lag of 2-4 weeks before
antidepressant effect occurs.
• Side effects & improved sleep occur
earlier (Suicide risk).
• 1st episode: Up to 1 year following
recovery.
• Repeat episodes: Up to 3 years (Royal
Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team
for Depression, 2004).
Stopping anti-d too early
can lead to relapse
Normal
Mood
Depression
requiring
treatment
2-4 weeks relief
depression
1-3 weeks sex drive, self
care, activity, memory
1st week
sleep
Begin antidepressant
anxiety
SSRIs available in Australia
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Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Indications SSRIs
• Mood disorders
• Anxiety disorders
Off label:
• Premature ejaculation
• Migraine headache,
• Diabetic neuropathy
• Fibromyalgia
SSRI’s Action
1.Normally serotonin,
a brain chemical is
released from a
nerve cell.
2.Serotonin is then
received by the next
nerve cell.
3.Some serotonin is
then reabsorbed into
the 1st nerve cell.
4.Not having enough
serotonin may be
associated with depression
& anxiety disorders.
SSRI’s block the reabsorbtion of serotonin into
the 1st nerve cell.
5.This blocking action results
in an increased amount of
serotonin being available at
the next nerve cell.
SSRI’s block reuptake of serotonin
into presynaptic neurone
Neurotransmitter
Re-uptake pump
Receptor
MAO
Dendrite
Axon
Synapse
Presynaptic storage vesicles
1st person account
• “Some people look upon medication
and/or therapy as some sort of life
sentence, but to me, the alternative is
a life sentence.” (Dietz, 2000, p. 37)
The hype of Prozac
Side-Effects: SSRI’s
• Common:
Nervousness &
anxiety, insomnia
(give dose in
morning), drowsiness
or fatigue, G.I nausea & diarrhoea,
loss of appetite,
weight loss, sexual
dysfunction.
Common Side Effects: SSRI
D ru g
S S R I's
C ita lo p ra m
F lu o x e tin e
F lu v o x a m in e
P a ro x e tin e
S e rtra lin e
D a ily
ra n g e m g
20 - 40
20 - 40
100 - 200
20 - 40
50 - 100
In s o
m n ia
Sex
D ys f.
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+++
+++
+++
+++
+++
A g it G .I.T W t
a tio n
g a in
+
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=
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++
++
++
++
0
0
0
+
0
Less common side effects
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Apathy
Extrapyramidal side effects (EPSEs)
Increased prolactin levels
Serotonin syndrome
Hyponatraemia
Bruising and bleeding Increased risk
of gastrointestinal bleeding (Loke, Trivedi, &
Singh, 2008).
Clinical response
• SSRI’s produce
a clinical
response much
more rapidly
than tricyclic
antidepressants.
True or False?
Serotonin syndrome
• Prevention: do not co-administer
SSRI’s and other drugs that increase
serotonin.
• Drug free interval before changing
from SSRI to other serotonin drugs.
Antidepressant
discontinuation symptoms
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F = flu like symptoms
I = insomnia
N = nausea
I = imbalance
S = sensory disturbances
H = hyperarousal (anxiety)
in Carson, 2000, p. 432)
(Gelenberg, 1998 cited
Advantages SSRI’s
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Minimal cardiac toxicity
Safe in overdose
Mild side effects
Non sedating
SSRI’s reduce overall suicide rates in
depressed patients significantly
more than tricyclic antidepressants.
True or False?
Tricyclic antidepressants:TCA’s
Axon
Dendrite
Dendrite
• Tricyclics block reuptake of noradrenaline & serotonin
into presynaptic neurone.
Tricyclics available in Australia
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Amitriptyline
Clomipramine
Dothiepin
Doxepin
Imipramine
Nortriptyline
Trimipramine
Indications
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Mood disorders
OCD
Panic disorder
Neuralgia (nerve pain) - best
available evidence is for amitriptyline
(Saarto & Wiffen, 2007)
• Nocturnal enuresis
TCA Action: 4 actions
1. Block presynaptic noradrenaline reuptake pump
(black lines).
2. Block the presynaptic serotonin reuptake pump
(red lines).
3. Block histamine receptors (yellow square) =
Sedative side effects.
4. Block post synaptic acetylcholine receptors (grey
square) = Dry mouth, confusion, memory
impairments, blurred vision.
• This blocking action results in an increased
amount of nor-epinephrine & serotonin being
available to the post synaptic neuron.
Side Effects: TCA’s
Common
• Sedation (give
dose at night)
• Dry mouth
• Blurred vision
• Weight gain
• Constipation
• Sweating.
TCA S/E.
Less common but important
• postural
hypotension
• urinary retention
• sexual dysfunction
• raised intra-ocular
pressure.
Side Effects: TCA’s
• Cardio-vascular effects in
people with cardiac disease.
• Impaired Cognitive function
in dementia.
• Precipitate a manic swing in
bipolar.
• May be fatal in O/D. Admit
ICU, cardiac monitor
Tetracyclics: Mianserin SE
• Common: as for TCA’s, plus vivid
dreams.
• Less common: anti-cholinergic
effects, plus jaundice, neutropenia,
agranulocytosis, effect glucose
tolerance & insulin levels
Tetracyclics: Mianserin SE
• Report sore
throat & flu like
symptoms.
• Regular blood
glucose tests.
• May be fatal in
O/D
Selective Serotonin and NorAdrenaline Reuptake Inhibitors
(SNRI)
Venlafaxine
• Low doses inhibits serotonin
• Medium dose inhibits nor-adrenaline
• High dose inhibits dopamine
• Nor-adrenergic drugs tend to have alerting
and energising effects
• Wide therapeutic index – tolerability
similar to SSRIs
• Monitor for elevated blood pressure on
high doses
Nor-adrenaline Reuptake
Inhibitor (NARI)
• NARI available in Australia
• Reboxetine
• Reasonable tolerability – similar to
TCAs
Enzyme inhibitors
• Mono-Amine Oxidase Inhibitors (MAOI) –
The first antidepressants discovered
• Alternative mechanism for increasing
synaptic availability of monoamines.
• MAOI & RIMA prevent intracellular
destruction of monamines by MAO
• MAOI’s available in Australia
• Phenelzine
• Tranylcypromine
MAOI & RIMA prevent intracellular
destruction of monamines by MAO
Neurotransmitter
Re-uptake pump
Receptor
MAO
Dendrite
Axon
Synapse
Presynaptic storage vesicles
Side Effects: MAOI’s
• Common: as for TCA’s, plus
agitation/excess stimulation (do not
give dose after 3 p.m.)
• Rare but serious: Hypertensive crisis
caused by ingesting tryramine
containing foods or a drug interaction
(cough & cold remedies, nasal drops
& sprays, diet pills, pethidine).
Side Effects: MAOI’s
• Prevention: Follow MAOI diet. Check
with Dr before using OTC
medication, notify Dr or dentist prior
to anaesthetic.
• Potential for abuse (amphetamine
like properties)
• Not well tolerated in > 65y
MAOI: Diet
• Avoid tyramine
containing foods (often
in foods requiring
aging): banana peel
(banana flavouring),
broad bean pods,
sauerkraut, matured
cheeses, aged meats,
smoked or pickled fish,
vegemite, brewers yeast.
MAOI: Diet
• Limited quantity:
raspberries,
avocado, soy
sauce,
commercial
soups, coffee
substitutes, wine,
port, beer,
chocolate.
Reversible Inhibitors of MonoAmine Oxidase type A (RIMA)
• RIMAs more selective than older MAOIs
• Do not cause serious dietary and drug
interactions (except at high doses).
• Have greater safety & tolerability
compared to MAOIs but are not as
effective in treatment resistant
depression.
RIMA available in Australia
• Moclobemide - Not effective for OCD
Receptor blockers:
Antagonists
• Noradrenergic and Specific Serotonergic
Antidepressant (NaSSA)
• Work by completely blocking (antagonist)
the serotonin and nor-adrenaline
receptors, preventing them from latching
on to serotonin and nor-adrenaline
(thereby allowing the neurotransmitters to
build up).
NaSSA available in Australia
• Mirtazapine
Debate
• What effect have
SSRIs had on
suicidal ideation,
attempts and
completed
suicide?
Summary
• Lag time 1 – 4/52 before initial response
• Newer antidepressants better tolerated,
safer in OD (less cardiotoxic)
• Caution in switching from 1 to another
(drug free intervals) to prevent serotonin
syndrome, P450 problems
• Continue for adequate time
• All anti-depressants can precipitate mania
• Increase psychomotor activity before
mood elevation (risk suicide)
References
Carson, V. B., (2000). Mental Health Nursing: The nurse patient
journal. (2nd ed.), Philadelphia: W. B. Saunders.
Dietz, M. (2000). Managing depression: A consumers view.
Australian Health Consumer, 3, 36-37.
Fortinash, K. M., & Holoday-Worret, P. A. (2000). Psychiatric mental
health nursing ( 2nd ed.). St. Louis: Mosby.
Galbraith, A., Bullock, S. & Manias, E. (2001). Fundamentals of
pharmacology (3rd ed.). Melbourne: Prentice Hall.
Hickie, I. (2000). An approach to managing depression in general
practice. Medical Journal of Australia, 173:106-110.
Loke, Y. K., Trivedi, A. N., & Singh, S. (2008). Meta-analysis:
Gastrointestinal bleeding due to interaction between selective
serotonin uptake inhibitors and non-steroidal anti-inflammatory
drugs. Alimentary Pharmacology & Therapeutics, 27(1), 31-40.
References
Mant, A., Rendle, V. A., Hall, W. D., Mitchell, P. B.,
Montgomery, W. S., McManus, P. R., et al. (2004).
Making new choices about antidepressants in
Australia: the long view 1975-2002. Medical Journal
of Australia, 181(7 Suppl), S21-24.
Nash, J., & Nutt, D. (2007). Antidepressants. Psychiatry,
6(7), 289-294.
Weitzel, C., & Jiwanlal, S. (2001). The darker side of
SSRIs. RN, 64(8), 43-48.