Schizophrenia

What is schizophrenia?

• chronic psychotic disorder = loss of reality

• characterised by psychosis, cognitive impairment and functional decline

• too much dopamine activity in brain + too little in other pathways

What is the mesolimbic pathway?

• increased dopamine levels leading to positive symptoms

What is the mesocortical pathway?

• decreased dopamine leading to negative symptoms

Causes of schizophrenia?

• genetic predisposition

• neurochemical imbalance

• environmental stress

• substance use

Types of schizophrenia?

• catatonic = change in movement/speech/imitating others

• disorganised = disturbance in behaviour and thought or speech

• paranoid = delusions, auditory hallucinations

• residual = previously diagnosed but no symptoms

Positive symptoms?

• hallucinations

• delusions

• disorganised speech

• disorganised behaviour

• slow / fast movement

Negative symptoms?

• lack of interest

• lack of motivation

• talking very little

• showing little / no emotion

• blank facial expression

• lack of drive

• avoid social contact

Cognitive symptoms?

• poor concentration

• memory issues

• inability to plan

• difficulty executing plan

DSM 5 criteria for diagnosis?

• 2 key symptoms (hallucinations/delusions/disorganised speech) = must be present for >1 month

• continuous signs of disorder lasting at least 6 months

• social or occupational dysfunction

• other causes excluded / substance/medical condition

What imaging and investigations can be carried out for diagnosis?

Imaging:

• CT / MRI / PET scan

Investigations:

• FBC, U+Es, LFTs, B12

• urine drug test

• HIV, syphilis

Treatment goals?

• reduce psychotic symptoms

• prevent relapse

• improve social and occupational function

• minimise adverse effects

Extrapyramidal symptoms (EPS)?

• painful muscle spams

• intense restlessness

• slow movements

• jerky movements

Monitoring before treatment?

• weight /BMI

• BP / pulse

• lipids

• glucose

Monitoring whilst on treatment?

• weight / glucose / lipids

• EPS

• adherence

• symptom control

• prolactin

• ECG (QT prolongation)

Examples of 1st generation antipsychotics?

• high potency = haloperidol, fluphenazine

• mid potency = perphenazine, loxapine

• low potency = chlorpromazine

How do first generation antipsychotics work?

• block dopamine D2 receptors in mesolimbic pathway to improve positive symptoms

• decrease dopamine in nigrostriatal and tuberoinfundibular pathway = leads to EPS and hyperprolactinaemia

Side effects of first generation antipsychotics?

• sedation

• hypotension

• weight gain

• amenorrhoea

• jaundice

What is hyperprolactinemia?

• increased levels of prolactin in the blood

• causes infertility and menstrual changes, milky nipple discharge and low libido

Which antipsychotic is hyperprolactinemia common in?

• risperidone

Examples of second generation antipsychotics?

• aripiprazole

• quetiapine

• olanzapine

• risperidone

• clozapine

How to second generation antipsychotics work?

• block dopamine and serotonin receptors

  • decreased dopamine in mesolimbic pathway = improves positive symptoms

  • increase dopamine in mesocortical pathway = improves negative and cognitive symptoms

• blocks serotonin receptors in nigrostriatal pathway = preserves dopamine therefore decreased risk of EPS

Side effects of second generation antipsychotics?

• weight gain

• sedation

• somnolence

• EPS

• hyperprolactinemia

• increased glucose

• anxiety

• headahce

Which antipsychotics have a high risk of metabolic side effects?

• olanzapine and clozapine

Which antipsychotics have a moderate risk of metabolic side effects?

• quetiapine and risperidone

Which antipsychotics have a low risk of metabolic side effects?

• aripiprazole, ziprasidone, and lurasidone

What are the metabolic side effects of antipsychotis?

• rapid weight gain

• diabetes

• dyslipidemia

What are long acting injectable antipsychotics and give examples

• IM injections every 2-3 weeks

• improvers adherence

• used in poor compliance / recurrent relapse

• examples:

  • risperidone

  • paliperidone

  • aripiprazole

What is treatment-resistant schizophrenia and how do u treat it?

• failure of >2 antipsychotics

• use clozapine

Adverse effects of clozapine?

• agranulocytosis

• seizures

• myocarditis

• severe constipation

Monitoring requirements for clozapine?

• WBC/neutrophils weekly for 18 weeks, fortnightly until 1 year, and monthly thereafter

  • if blood test missed - stop pharmacy supply

• BP /pulse rate

• BMI

• ECG

Which antipsychotics are safe in pregnancy?

• quetiapine

• aripiprazole c

• olanzapine

• lurasidone

Common drug-drug interactions of antipsychotics?

• Sedating Agents (Alcohol, Benzodiazepines, Opioids): Significantly increase drowsiness, sedation, and risk of respiratory depression.

• Antihypertensives - Combine to cause profound dizziness, falls, and severe drops in blood pressure (orthostatic hypotension), especially with Clozapine, Quetiapine, or Risperidone.

• QT-Prolonging Drugs - increase risk of arrhythmia

Duration of treatment?

• at least 6 months after acute episode

• if another episode occurs = may need medication for further 2-5yrs

• if multiple episodes = medication for lifelong

Relapse prevention plan?

• identify triggers

• recognise early symptoms and makers of relapse

• who to call in crisis

• lifestyle changes

Lifestyle management?

• balanced diet - high fiber food, fruits and veg

• regular meals - keep blood sugar stable

• exercise - reduce stress and improve sleep

• hydration

• smoking cessation

• avoid alcohol and drugs

• sleep hygiene