Antidepressants

1
Antidepressants

• Sue Henderson

2
Clinical Indications

• Mood disorders
• Anxiety disorders
• Eating disorders
• Chronic pain
• Incontinence

3
Personal perspective

• I dont 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)

4
Use of antidepressants in the Australian
population, 19752002
(Mant et al., 2004)
5
Classes of antidepressant as proportion of total
sales of antidepressants in the Australian
population, 19902002
(Mant et al., 2004)
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Utilisation of top-selling antidepressants in
the Australian population, 19902002
(Mant et al., 2004)
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Major and sub-classes

• Based on 3 physiological actions
• 1. Reuptake inhibition
• 2. Enzyme inhibition
• 3. Receptor blockade
• (Nash Nutt, 2007).

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Reuptake inhibitors

• Selective Serotonin Reuptake Inhibitors( SSRI)
• Tricyclic Antidepressants (TCAs)
• Selective Serotonin and Nor-Adrenaline Reuptake
  Inhibitors (SNRI)
• Nor-adrenaline Reuptake Inhibitor (NARI)

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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)

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Receptor blockers

• Nor-adrenergic and Specific Serotonin
  Antidepressants (NaSSA) work by blocking
  receptors.

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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).

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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 anxiety
sleep
Begin anti-depressant
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SSRIs available in Australia

• Citalopram
• Escitalopram
• Fluoxetine
• Fluvoxamine
• Paroxetine
• Sertraline

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Indications SSRIs

• Mood disorders
• Anxiety disorders
• Off label
• Premature ejaculation
• Migraine headache,
• Diabetic neuropathy
• Fibromyalgia

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SSRIs 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.

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• 4.Not having enough serotonin may be associated
  with depression anxiety disorders. SSRIs
  block the re-absorbtion 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.

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SSRIs block reuptake of serotonin into
presynaptic neurone
Synapse
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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)

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The hype of Prozac
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Side-Effects SSRIs

• Common Nervousness anxiety, insomnia (give
  dose in morning), drowsiness or fatigue, G.I -
  nausea diarrhoea, loss of appetite, weight
  loss, sexual dysfunction.

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Common Side Effects SSRI
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Less common side effects

• Apathy
• Extrapyramidal side effects (EPSEs)
• Increased prolactin levels
• Serotonin syndrome
• Hyponatraemia
• Bruising and bleeding Increased risk of
  gastrointestinal bleeding (Loke, Trivedi,
  Singh, 2008).

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Clinical response

• SSRIs produce a clinical response much more
  rapidly than tricyclic anti-depressants. True or
  False?

24
Serotonin syndrome

• Prevention do not co-administer SSRIs and other
  drugs that increase serotonin.
• Drug free interval before changing from SSRI to
  other serotonin drugs.

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Antidepressant discontinuation symptoms

• F flu like symptoms
• I insomnia
• N nausea
• I imbalance
• S sensory disturbances
• H hyperarousal (anxiety) (Gelenberg, 1998 cited
  in Carson, 2000, p. 432)

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Advantages SSRIs

• Minimal cardiac toxicity
• Safe in overdose
• Mild side effects
• Non sedating
• SSRIs reduce overall suicide rates in depressed
  patients significantly more than tricyclic
  antidepressants. True or False?

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Tricyclic antidepressantsTCAs
Dendrite

• Tricyclics block reuptake of noradrenaline
  serotonin into presynaptic neurone.

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Tricyclics available in Australia

• Amitriptyline
• Clomipramine
• Dothiepin
• Doxepin
• Imipramine
• Nortriptyline
• Trimipramine

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Indications

• Mood disorders
• OCD
• Panic disorder
• Neuralgia (nerve pain) - best available evidence
  is for amitriptyline (Saarto Wiffen, 2007)
• Nocturnal enuresis

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TCA Action 4 actions

• Block presynaptic noradrenaline reuptake pump
  (black lines).
• Block the presynaptic serotonin reuptake pump
  (red lines).
• Block histamine receptors (yellow square)
  Sedative side effects.
• 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.

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Side Effects TCAs Common

• Sedation (give dose at night)
• Dry mouth
• Blurred vision
• Weight gain
• Constipation
• Sweating.

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TCA S/E. Less common but important

• postural hypotension
• urinary retention
• sexual dysfunction
• raised intra-ocular pressure.

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Side Effects TCAs

• 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

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Tetracyclics Mianserin SE

• Common as for TCAs, plus vivid dreams.
• Less common anti-cholinergic effects, plus
  jaundice, neutropenia, agranulocytosis, effect
  glucose tolerance insulin levels

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Tetracyclics Mianserin SE

• Report sore throat flu like symptoms.
• Regular blood glucose tests.
• May be fatal in O/D

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Selective Serotonin and Nor-Adrenaline 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

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Nor-adrenaline Reuptake Inhibitor (NARI)

• NARI available in Australia
• Reboxetine
• Reasonable tolerability similar to TCAs

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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
• MAOIs available in Australia
• Phenelzine
• Tranylcypromine

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MAOI RIMA prevent intracellular destruction of
monamines by MAO
Synapse
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Side Effects MAOIs

• Common as for TCAs, 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).

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Side Effects MAOIs

• 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 gt 65y

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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.

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MAOI Diet

• Limited quantity raspberries, avocado, soy
  sauce, commercial soups, coffee substitutes,
  wine, port, beer, chocolate.

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Reversible Inhibitors of Mono-Amine 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

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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

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Debate

• What effect have SSRIs had on suicidal ideation,
  attempts and completed suicide?

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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)

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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, 173106-110.
• 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.

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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.