Anti-depressants

1
Anti-depressants

• Or What When
• Dr Bruce Davies

2
Range

• Tricyclics
• Tetracyclics
• SSRI
• SNRI
• MAOI
• Oddities
• Adjuvants

3
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

4
Drug Failure

• Non compliance.
• Inadequate dosage.
• Other drugs e.g. alcohol, caffeine.
• Unresolved outside problems.
• Up to 25 failure even if above dont apply.

5
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

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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

7
Tricyclics

• Lofepramine
• Least toxic TCA.
• Minimal sedative side effects.
• Anticholinergic
• Doubts about efficacy.
• 210 mg / day

• Protriptyline
• Stimulant.
• Anticholinergic
• 40mg / day

8
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

9
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.

?
10
SSRI
Citalopram Few interactions Most expensive 20 mg /day
Fluoxetine Sedation Skin s/e Anxiety Cheapest 20-80 mg /day
Fluvoxamine Gut s/e Insomnia - 200 mg /day
Paroxetine Sedation Withdrawal problems ? 20 mg /day
Sertraline Diarrhoea 50 mg /day
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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.

12
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.

13
Oddities

• Trazodone.
• Unique structure.
• Low cardiotoxicity, few anticholinergic side
  effects.
• Drowsiness .
• Nausea.
• 150 mg /day.

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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

15
Adjuvants and Combinations

• Realm of specialists
• Lithium, carbamazepine
• Mixtures i.e. SSRI and TCA
• Dangerous need expert supervision

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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.

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Anxiety

• ? Role of benzodiazepines.
• ? Beta-blockers.
• Buspirone.
• Some efficacy, but small.
• Slow onset, 2-4 weeks.

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DSM - IV
Duration gt 2 weeks
Depressed mood or Marked loss of interest
or pleasure in normal activities
Plus 4 of

1. Significant change in weight
2. Significant change in sleep pattern
3. Agitation or retardation
4. Fatigue or loss of energy
5. Guilt / worthlessness
6. Cant concentrate or make decisions
7. Thoughts of death or suicide

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Incidence Of Depression 2000 Patients
100 - major
100 - minor
200 - subclinical
Depression. In 50 of patients it may not be
acknowledged.
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ICD - 10

• Patient has low mood
• How bad is it and how long has it been going on?
• Have you lost interest in things?
• Are you more tired than usual?
• If the answer is yes to these, then
• Have you lost confidence in yourself?
• Do you feel guilty about things?
• Concentration difficulties?
• Sleeping problems?
• Change in appetite or weight?
• Do you feel that life is not worth living any
  more?

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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.

22
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.

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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.