Neuroleptics/ Antipsychotics

Neuroleptics/ Antipsychotics

1. Background

   • Major breakthrough in medicine because it allowed peoples behaviour to be controlled in a way which wasn't possible before. They were able to be released from hospital which wasn't previously possible.
   • Dark side: ALWAYS have significant, debilitating side effects
   • Commonly overused at present- as they are used for bipolar which is commonly diagnosed
   • History
     • 1950: chlorpromazine
     • 1958: haloperidol - most potent
     • Flupenthixol: Long acting injection --> last for 3 to 4 weeks, good for people with long term psychotic illnesses who are unable to take regular tablets/ medicine
     • Risperidone: early 1990s. First of the class called 'atypical antipsychotics' --> took over the market despite being worse than the previous drugs.
   • Antipsychotics: American name which developed later in the issue of these drugs. First discovered in France as neuroleptics
   • Neuroleptics = hols the nervous system in constant state
   • Antipsychotics: implies drug works against psychosis which isn't true, better name would be 'major tranquillisers'

2. Major Therapeutic effects

   • The first antipsychotic was used for anasthesia, to prevent vomiting.
   • It has the effect of calming agitation, however not though sedation
   • Reduces behavioural activity, even when the patient is not sleepy
   • Some of them make patients sleepy, haloperidol doesn't.
   • "Induces a state of psychic indifference" Healey, makes you tranquil
     • Does this by blunting emotion - fear is less strong, happiness is less strong = emotionally indifferent
   • Dose dependent 'Parkinsonism' -> muscles become very stiff
   • When people are psychotic they experience hallucination and delusions --> antipsychotics blunt these e.g. person continues to hear voices but doesn't listen to them. They lose their power to influence the persons behaviour.
   • Makes catatonia worse

3. Mechanisms of action

   • Dopamine D2 receptor blockers
   • Dopamine has several types of receptor, D2 is the main one.
   • Diminish central dopamine activity in the meso-limbic dopamine system (causes motivation)
   • If you stimulate the meso-limbic dopamine system you are more motivated, if you block it with anti-psychotics you are less motivated
   • Atypical neuroleptics e.g. risperidone --> weakens D2, plus S2 receptor blockers. Usually less neuroleptic, and cause more sedation, weight gain and metabolic problems (e.g. diabetes)

4. Clinical uses

   • 1. Used in schizophrenia, mania, psychotic major depressive disorder
   • 2. Calming agitation from any cause
   • 3. Suppress undesired behaviour (along with all forms motivated behaviour) in demented and delirious old people e.g. nursing homes and non-psychotic violent people
   • 4. Now prescribed as 'mood stabilisers' in bipolar disorder, including children, suppresses hyperactive behaviour. Increasing rates of prescription, including in children and teens.

5. Side effects

   • 1. Dysphoric: make many people 'feel bad', patients often dislike taking them = not abused. All patients experience 'negative symptoms', demotivation, emotional blunting, anhedonia, asocial. Akathisia - inner turmoil and agitation - can provoke suicide.
   • 2. Long-term usage creates dependence - too rapid withdrawal causes psychotic breakdown.
   • 3. 'Dyskenesias' = abnormal movements (rigidity, terror, tongue protrusion, upward gaze). Tardive dyskinesia is often permanent ie.e. brain damage
   • 4. Increased death rate: partly from suicide, partly from many other causes related to metabolism and nervous system functioning