Mental Health Medicines

1
Mental HealthMedicines

• Peter Pratt
• Chief Pharmacist
• Sheffield Health and Social care NHS Foundation
  Trust

Tuesday 4th August 2009
2
The early 1950s
3
Treatment
4
The pharmacy
5
1945 Exciting new treatments

• Lithium Cade

6
John Cade

• Australian Psychiatrist
• Taken Japanese Prisoner of War
• Nearly 4 years Changi Prison
• Bundoora Hospital near Melbourn
• ."I believe the brain, like any other organ, can
  get sick and it can also heal.
• Madness (mania) is caused by excess of
  chemicals
• Search for the substance in urine

7
The Experiment(s)
8
The Result

• 1949 The First new treatment for psychotic
  excitement
• Cade, JFJ Lithium salts in the treatment of
  psychotic excitement. Med J Aust 1949, 36,
  p349-352

9
The Rest of the world

• BAN this toxic substance
• Time magazine (Monday, Feb. 28, 1949 )
• Mogen Schou 1960s
• Amdi Amdisen 1970s

10
50 years later

• 2006 NICE Guidelines for Bipolar disorder
• LITHIUM , olanzapine or valproate should be
  considered for long-term treatment of bipolar
  disorder.
• The choice should depend on
• ..the patients preference.

11
More Exciting News - Psychosis

• 1951
• Chorpromazine
• Henri Laborit
• Antihistamine - Anaesthetic cocktail sedation
• 1952
• Delay Deniker discovered the antipsychotic
  effects
• Marketed as Largactil Large actions

12
The race is on.
Aliphatic phenothiazine
Piperidine phenothiazine
Chlorpromazine
Piperizine phenothiazine
Butyrophenone
Dibenzodiazepine
13
The race continued..
14
Drugs dont cure schizophrenia

• Control/relive/suppress symptoms
• Hallucinations
• Delusions
• Special reference
• Distress
• 25 respond very well
• Up to 40/50 respond partially
• 30 dont respond

15
Downsides appear

• Side effect/Adverse effects
• Deaths (clozapine withdrawn)
• Stiffness
• Restlessness
• Slowness (Bradykinesia)
• Parkinsonism( Shaking)
• Skin sensitivity
• Dry Mouth, urinary retention, blurred vision
• Sexual dysfunction

16
1960s - 1970s

• More Drugs Better response
• Discovering Pharmacokinetics
• Problems of absorbtion
• People stop taking drugs Relapse
• Develop depots

17
1980s

• The penny drops
• 25 respond very well
• Up to 40/50 respond partially
• 30 dont respond
• New(er) and Better drugs needed

18
1980s

• John Kane (re)discovered clozapine
• Treatment resistant schizophrenia
• NO movement problems (extra pyramidal side
  effects) BUT
• Problems with white blood cells
  (agranulocytocis)
• Must take weekly blood tests
• Problems with epilepsy
• Problems with drooling
• Problems with weight gain
• Problems with severe constipation (deaths have
  occurred)
• Best NEW drug in psychiatry since 1950 ??
• (big problems with Finance VERY EXPENSIVE)

19
The Race is on

• So called Atypical era
• Cannot deny mental health patients
  modern/expensive drugs
• Drug industry pushing No side effects
• Reality different side effects
• Fewer problems with movement disorders
• But may cause more weight gain, diabetes, heart
  problems, lipids Increased risk of stroke in
  older people

20
50 years later.Nice Schizophrenia 2009

• Take account of patients concerns
• Consider every patient as an individual
• Challenges drug industry view that atypicals
  are better for everyone
• But they do offer more CHOICE
• Clozapine still best if other antipsychotics
  dont work

21
What about Depression?

• Depression Major depression can be fatal
• Beyond the norm of sadness
• Poor sleep, Poor appetite, Feeling worthless
  cannot, see any future thoughts of self
  harm/suicide

22
Depression in 1950s

• ECT
• Left over Hydrazine (v2) rocket fuel
• Hoffman La Roche - Iproniazid Treatment for TB
  Patients became happy
• Hepatotoxic (liver problems) - isocarboxazid
  phenelzine
• Formulated MAO theory of depression

23
More developments late 50s

• Ciba Geigy looking for new phenothiazine
  (antipsychotic)
• Discovered antidepressant effects of Imipramine

chlorpromazine
imipramine
24
The race is on..
Amitriptyline
Imipramine
Clomipramine
Dosulepin
25
Downsides appear

• Only 70 respond
• 30 non response (but 30 placebo)
• Slight response in first week
• Increased risk of suicide
• Highly toxic (in overdose)
• Dry mouth ,constipation, cardiac effects
• Better drugs needed !

26
1980s newer antidepressants

• The SSRIs
• Eg Fluoxetine (prozac)
• Less toxic in O/D
• Less antimuscarinic s/e
• expensive
• New race begins
• The newspapers say.
• NICE says.

27
Pharmacy Mental Health 2020
28
Forget Dopamine its glutamate
"Analysts have hailed LY2140023 (a NMDA glutamate
receptor agonist glutamate) as an exciting new
medicine that may herald the arrival of
third-generation antipsychotic drugs."
29
A personal view

• New drugs breakthrough possible but unlikely
• Our challenge - Using existing drugs better
• Listening to patients
• Medicines management as a partnership
• Medicines reconciliation Simply getting correct
  information may help!
• In the future greater knowledge of genetics
  (Pharmacogenomics ) may help us to individualise
  some pharmacological treatments
• Cost/rationing may become an issue