Transcript Anti-depressants

Anti-depressants
Or What When
Dr Bruce Davies
Range
 Tricyclics
 Tetracyclics
 SSRI
 SNRI
 MAOI
 Oddities
 Adjuvants
Factors Influencing Choice
 Features of illness, e.g.
agitation, hypersomia
 Suicide risk
 Other therapy
 Other illness.
 Side effects
 Cost
 Special problems e.g.
Age, driving,
pregnancy
Drug Failure
 Non compliance.
 Inadequate dosage.
 Other drugs e.g. alcohol, caffeine.
 Unresolved outside problems.
 Up to 25% failure even if above don’t
apply.
Tricyclics
Amitryptyline
 Potent sedative
 Weight gain ++
 Anticholinergic ++
 Most researched
 150mg / day
(Therapeutic in 95% of
adults)
Clomipramine
 Similar side effects to
amitryptyline.
 Said to be best for
obsessional symptoms.
 150mg / day
Tricyclics
Dothiepin
 Sedative
 Same side effects as
amitryptyline.
 By far and away the
most toxic
antidepressant.
 150 mg / day
Imipramine
 Stimulant
 Anticholinergic ++
 150 mg/ day
Tricyclics
Lofepramine
 Least toxic TCA.
 Minimal sedative side
effects.
 Anticholinergic +
 Doubts about efficacy.
 210 mg / day
Protriptyline
 Stimulant.
 Anticholinergic +
 40mg / day
Tetracyclics
Maprotiline
 Similar side effect
profile to
amitryptyline.
 Seizures severe in
overdose.
 150 mg /day
Mianserin
 Good safety in
overdose.
 Few sedative or
anticholinergic
properties.
 ? Agranulocytosis risk
 90 mg / day
SSRI
 First choice in elderly.
 First choice if heart
disease.
 First choice if suicide
risk.
 More expensive.
?
Side effects
 Like TCA reduce with
time.
 Gut problems
predominate.
 Flat dose response
curve – so no need to
titrate dose upwards.
SSRI
Citalopram
Few
interactions
Fluoxetine
Sedation –
Skin s/e
Fluvoxamine Gut s/e +
Most
expensive
Anxiety +
Cheapest
Insomnia -
20 mg /day
Paroxetine
Sedation +
Sertraline
Diarrhoea
Withdrawal 20 mg /day
problems ?
50 mg /day
20-80 mg
/day
200 mg /day
SSNRI
Venlafaxine
 Selective Serotonin and noradrenaline
reuptake inhibitor – like amitryptyline.
 Few other effects – unlike amitryptyline.
 75-150mg / day minimum
 Dry mouth, somnolence, high BP, nausea,
headache and dizziness.
MAOI
 The old ones block peripheral MAOI ( B )
and central MAOI (A) so a low tyramine
diet is needed. ? Obsolete.
Moclobemide.
 Only MAOI-A.
 ? Role.
 ? Special place in anxiety disorder.
 300-600mg / day.
Oddities
Trazodone.
 Unique structure.
 Low cardiotoxicity, few anticholinergic
side effects.
 Drowsiness +.
 Nausea.
 150 mg /day.
Oddities
Tryptophan
 Natural amino acid - Serotonin precursor.
 Eosinophilia-myalgia syndrome, Hospital
initiation only.
 Adjuvant to others ?
Flupenthixol
 Some doubts as to efficacy.
 Fast action
 1 mg / day
Adjuvants and Combinations
 Realm of specialists
 Lithium,
carbamazepine
 Mixtures i.e. SSRI and
TCA
 Dangerous – need
expert supervision
Anxiety
 Usually worth trying a
antidepressant.
 May be useful to avoid the
stimulant ones !
 May need higher doses.
 Initiation may lead to
paradoxical increase in
symptoms. ? Cover with
short course of anxiolytic.
Anxiety
 ? Role of
benzodiazepines.
 ? Beta-blockers.
Buspirone.
 Some efficacy, but
small.
 Slow onset, 2-4
weeks.
DSM - IV
Duration > 2 weeks
Depressed mood
or Marked loss of interest or
pleasure in normal activities
Plus 4 of:
i. Significant change in weight
ii. Significant change in sleep pattern
iii. Agitation or retardation
iv. Fatigue or loss of energy
v. Guilt / worthlessness
vi. Can’t concentrate or make decisions
vii. Thoughts of death or suicide
Incidence Of Depression : 2000
Patients
100 - major
100 - minor
200 - subclinical
Depression. In 50% of patients it may
not be acknowledged.
ICD - 10
Patient has low mood:
1) How bad is it and how long has it been going on?
2) Have you lost interest in things?
3) Are you more tired than usual?
If the answer is yes to these, then:
4) Have you lost confidence in yourself?
5) Do you feel guilty about things?
6) Concentration difficulties?
7) Sleeping problems?
8) Change in appetite or weight?
9) Do you feel that life is not worth living any more?
ICD - 10
 Mild
Two criteria from 1-3 and 2 others.
 Moderate
Two criteria from 1-3 and 3-4 others or a yes
to question 5.
 Severe
Most of the criteria in severe form especially
questions 5 & 9.
BUT BUT BUT
 But there is a lot more
than the drugs.
 The use of other
therapies is equally
important.
 The doctor may be the
best drug.
 Availability is often
the limit to other
treatment methods.
Based On
 BNF June 2000.
 Depression in General Practice. Tylee,
Priest & Roberts. Pub. Martin Dunitz. 1996.
 GP Psychotropic Handbook. S Bazire.
Quay Books. 1995.
 Basic Notes in Psychiatry. Michael Levi.
Kluwer Books. 1997.