Treatment of Psychosis

• Early intervention improves outcome, reduces disruption/trauma („collateral damage‟), etc. Important given stage of life (adolescence) and the potential problems for subsequent social and occupational development etc

• Treatment programme involving health professionals, family members, support agencies, and cultural/community context

• Brain‟s ability to process and interpret information is affected Þ think carefully about how information conveyed is received. Keeps the facts simple, avoid distractions and pressure, ask one question at a time, give plenty of time to answer

• Biological treatment: treat early, immediately if psychotic, key issue with maintenance medication is compliance

• Psychological: supportive, education, self-care skills. Social skills training and community integration skills ® overcome withdrawal ® significant ¯ in readmissions

• Social: assertive (to combat stigma), community care

• Relapse prevention: understanding drugs, warning signs, prognosis, side effects

Antipsychotic Medication

• Neuroleptics or major tranquillisers
• May also use lithium, carbamazepine, antidepressants and benzodiazepines for psychosis
• Reduced risk of relapse in schizophrenia, but 40% will still relapse within a year
• Two effects:
  • Reduces delusions and hallucinations (may take 1 –2 weeks)
  • Tranquillising/calming effect (¯acute agitation, immediate effect)
• For first presentation, treat with low dose and use atypicals (¯side effects ® ­compliance). Use adjunctive long acting benzodiazepine for first few weeks to sedate and ¯agitation
• Can be administered orally, IM, IV and some as depot (but not yet for atypicals)
• Side effects range over sedation, extra-pyramidal, anti-cholinergic and hypotensive
• All relatively effective at reducing positive symptoms, but „atypicals‟ better than „typicals‟ at reducing negative symptoms (eg ¯motivation, interest, lack of emotional display, restricted speech)
• All have hepatic elimination

Typicals (ie Older antipsychotics)

• Mode of action: block dopamine (D2) receptors. Most also have low affinity for 5HT2 receptors. Varying amounts of anticholinergic, antihistamine and anti a-1 effects
• Adverse Effects:
  • Extrapyramidal Syndromes (EPS):
    • Acute: Occur early in treatment – usually first two months.
    • Dystonias (muscle cramps and spasms): treat with benztropine parenterally 

• Akathisia (restlessness): treat with b blocker or benzodiazepine 
• Parkinsonism (tremor, cog wheel rigidity, bradykinesia, mask like face) – may improve with time 
• Anticholinergics only indicated in those whose antipsychotic dose cannot be safely reduced. (= antiparkinsonian medication, eg antimuscarinic drugs such as Cogentin)
• Tardive Dyskinesia: 
  • Late onset dyskinetic syndrome due to antipsychotic drug treatment. Usually months or years after treatment
  • Fairly common: 15 – 30% 
  • Slow, repetitive involuntary movements of mouth/face, and maybe limbs and trunk. Disappear during sleep
  • Risk factors: old age, organic brain disease, negative symptoms, alcohol abuse
  • Irreversible in 50%
  • No established protocol for treatment: try dose reduction, lithium, or change to clozapine
  • Made worse by dopaminergic agonists and anticholinergics
• Other effects:
  • Sedation
  • Anticholinergic effects (dry mouth, constipation, blurred vision, urinary hesitancy) 
  • a blockade (postural hypotension, tachycardia, delayed ejaculation)
  • Endocrine effects (­PRL, marked weight gain, ¯libido, impotence, amenorrhoea) 
• Neuroleptic Malignant Syndrome: Rare (0.2 – 1%) with hyperthermia, rigidity, and impaired consciousness. 20% mortality. Emergency treatment (cooling, fluids, etc)

• Interactions:
  • Potentiate sedation with hypnotics, alcohol, opioid analgesics
  • Fluoxetine increases risk of EPS

Atypicals

• Clozapine:

• Mode of action: numerous receptors: D1, D2, D4, 5HT2, blocks a-1, H1 and muscarinic receptors
  • Effective in individuals not responsive to classical antipsychotics, effective for positive and negative symptoms, no extrapyramidal side effects, no impact on sexual or reproductive function.
  • Side effects:
    • Sedation, tachycardia, constipation, weight gain, and seizures (3% at highest dose) 
    • Agranulocytosis/blood dyscrasias in 1-2 % by 1 year, most in first 18 weeks ® regular blood tests 
    • Potent enzyme inhibitor: significant drug interaction potential
    • Serotonergic crisis with SSRIs
    • Hypersensitivity syndrome: PUO, arthritis, rash
    • Prolongation of QT
    • Myocarditis

• Risperidone:
  • Mode of action: binds to 5HT2 and D2 receptors, antagonises H and a-1 receptors 
  • Similar efficacy as other antipsychotics for positive symptoms. Effective for negative side effects and also affective symptoms (depression, anxiety). 
  • Some dose related extrapyramidal side effects. ­PRL at high doses. Also insomnia, agitation, anxiety, headache

• Olanzapine:
  • Mode of action. Similar to clozapine.  Like clozapine has minimal impact on PRL
  • Similar efficacy to haloperidol, but more impact on negative symptoms
  • Sedation, headache, dizziness, constipation, dry mouth, weight gain