Treatment of Psychosis

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:

o  Reduces delusions and hallucinations (may take 1 –2 weeks)

o  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:

o   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)

o   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

o   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) 

o   Neuroleptic Malignant Syndrome: Rare (0.2 – 1%) with hyperthermia, rigidity, and impaired consciousness. 20% mortality. Emergency treatment (cooling, fluids, etc)

·        Interactions:

o   Potentiate sedation with hypnotics, alcohol, opioid analgesics

o   Fluoxetine increases risk of EPS

Atypicals

·        Clozapine:

·        Mode of action: numerous receptors: D1, D2, D4, 5HT2, blocks a-1, H1 and muscarinic receptors

o   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.

o  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:

o  Mode of action: binds to 5HT2 and D2 receptors, antagonises H and a-1 receptors 

o  Similar efficacy as other antipsychotics for positive symptoms. Effective for negative side effects and also affective symptoms (depression, anxiety). 

o  Some dose related extrapyramidal side effects. ­PRL at high doses. Also insomnia, agitation, anxiety, headache

·        Olanzapine:

o  Mode of action. Similar to clozapine.  Like clozapine has minimal impact on PRL

o  Similar efficacy to haloperidol, but more impact on negative symptoms

o  Sedation, headache, dizziness, constipation, dry mouth, weight gain