L12 Schizophrenia Flashcards
Define ‘psychosis’.
Refers to an acute & severe mental condition:
- Being out of touch with reality; disordered thought process, beliefs, perceptions
- Lack of insight from affected individual
Define ‘schizophrenia’.
1) One of the more common forms of psychosis
2) Heterogenous syndrome of disorganised & bizarre thoughts, delusions, hallucinations, inappropriate affect & impaired psychological functioning:
- Delusions: fixated forced belief that doesn’t change despite repeated correction & NOT based in reality.
- Hallucinations: auditory (most common), visual, tactile, olfactory & gustatory
3) Onset commonly in late adolescence to early adulthood
- Males: Usually early 20s
- Females: Usually late 20s to early 30s
What are some pharmacological agents that may be associated with psychotic symptoms as adverse side effects?
1) Dopamine agonists (e.g. levodopa & bromocriptine)
2) Excessive corticosteroids
3) Thyroid hormones
4) Alcohol
5) Psychoactive substance abuse (e.g. BZDs, barbiturates, CNS stimulants & hallucinogens)
6) Antidepressants
7) Beta-blockers (e.g. propranolol)
Lead to mania & potentially precipitate psychosis.
What is the primary pathophysiological abnormality influencing the etiology of schizophrenia?
Dysregulation of one of the three main neurotransmitters function:
1) Dopaminergic (DA)
2) Serotonergic (5-HT)
3) Glutamatergic
What is the mechanism of action of typical / first-generation antipsychotics (FGA)?
Dopaminergic D2 receptor antagonism
What is the most common mechanism of action of atypical / second-generation antipsychotics (SGA)?
Serotonergic (5-HT2A) & dopaminergic (D4»D2) receptor antagonisms as core MOA
- Not all SGA work via this mechanism though.
What are some predisposing factors that may increase the vulnerability of an individual to precipitate schizophrenia?
GENPP:
1) Genetics
2) Environment in utero
3) Neurodevelopment effects
4) Personality
5) Physical, psychological & social factors in infancy & early childhood
What are some precipitating factors that may increase the risk of an individual manifesting symptoms of schizophrenia?
C-PED:
1) Cerebral tumours or injury
2) Personal misfortune
3) Environment of highly expressed emotion
4) Drugs
- Alcohol, BZDs, barbiturates, antidepressants, corticosteroids, CNS stimulants, hallucinogens, BBs (e.g. propranolol) & dopamine agonists (e.g. levodopa & bromocriptine)
What are some perpetuating factors that may prolong the course of schizophrenia?
PLSS:
1) Poor adherence w/ antipsychotic medications
2) Lack of support / Poor socioeconomic status or environment
3) Social withdrawal
4) Secondary demoralisation
Based on the DSM-5 criteria for diagnosis of schizophrenia, describe the clinical presentation of an individual symptomatic of schizophrenia.
1) At least 2 of the following smx (i.e. 4 positive e.g. + negative smx), each persisting for a significant portion of at least 1-month period:
- Delusions that are persecutory in nature
- Hallucinations
- Disorganised speech manifested from tangential thought process OR slurred, unrecognisable speech patterns (e.g. mm, ah, uh)
- Grossly disorganised OR catatonic behaviour (medical emergency!!)
- Negative symptoms (e.g. affecting flattening of emotions, avolition/loss of motivation)
2) Social/occupation dysfunction
3) Duration: Continuous signs of disorders for at least 6 months
- Inclusive of at least 1 month of criteria 1 symptoms
- May include prodromal or residual symptoms
4) Schizoaffective or mood disorder has been EXCLUDED
5) NOT due to underlying medical disorder or substance abuse
6) If Hx of pervasive development disorder present, symptoms of hallucinations or delusion MUST be present for at least 1 month
What are two important screening questions to ask psychiatric patients in evaluating the efficacy and tolerability of their antipsychotic Tx?
1) Adherence to medication?
- To be reassessed on every visit.
2) Any suicidal/homicidal ideations & risks?
- Conduct mental state exam (MSE) for accurate diagnosis, including suicidality risk!
- Reassess MSE on every interview to evaluate efficacy & tolerability to antipsychotic medications.
What lab parameters should be investigated to exclude other differential diagnoses from schizophrenia?
- Vitals, weight & BMI
- FBC (WBC in particular for infections e.g. meningitis/encephalitis/neurosyphillis)
- Renal panel: Urea, electrolyte, creatinine
- LFTs
- TFTs (thyroid) for hypothyroidism
- ECG for CV risk
- Folate & Vit B12 for anemia
- Fasting blood glucose for hypoglycemia & diabetes
- Lipid panel for CV risk
- Urine toxicology for substance misuse & pregnancy
To exclude general medical conditions or substance-induced symptoms e.g. psychosis / depression / mania / anxiety / insomnia
What are some non-pharmacological recommendations to manage patients diagnosed with schizophrenia?
1) Individual Cognitive Behavioural Therapy (CBT)
- Primarily used in anxiety disorders
- Used in conjunction w/ antipsychotic medications & family intervention
- Applicable for (a) preventing psychosis in “at risk” group (b) first-episode psychosis to assess for PTSD (c) schizophrenia
- However, it is difficult to counsel highly irrational & aggressive pt. w/ schizophrenia!!
2) Neurostimulation
- Electroconvulsive Treatment (ECT): Reserved for treatment-resistant schizophrenia
- Repetitive Transcranial Magnetic Stimulation (rTMS): Effective for reducing auditory hallucinations in schizophrenia
3) Psychosocial rehabilitation programs: to improve patient’s adaptive functioning
- Individual: Supportive/counselling, personal therapy, social skills therapies, vocational sheltered (esp. for males)
- Group: Interactive/social
- Cognitive Behavioural: CBT, adherence/compliance therapy
What are the therapeutic goals in the treatment of schizophrenia?
1) Acute Stabilisation:
- Minimise threat to self and others; may require physical / forceful interventions during acute aggressive psychosis
- Minimise acute symptoms i.e. agitation, aggression, hostility, sleep improvement
- Improve role functioning (NOT to pre-morbid levels, BUT to function sufficiently)
- Identify appropriate psychosocial interventions (e.g. increased awareness of +ve & -ve symptoms & how to manage)
- Collaborate w/ family & caregivers for support
2) Stabilisation
- Minimise / prevent relapse
- Promote medication adherence
- Optimise dose vs adverse effects
3) Stable / Maintenance Phase
- Improve functioning & quality of life
- Maintain baseline functioning
- Optimise dose vs adverse effects
- Monitor for prodromal smx of relapse
- Monitor for adverse effects of antipsychotic medications (e.g. tardive dyskinesia)
Why are antipsychotic drugs used in the treatment of schizophrenia?
1) Relieve symptoms of psychosis e.g. thought disorders, hallucinations & delusions, thus preventing relapse
- Usually less effective in apathetic withdrawn patients
- Pt. w/ acute symptoms of schizophrenia generally respond better than those w/ chronic symptoms
2) Long-term Tx often necessary after 1st episode of psychosis & prevent illness from becoming chronic
- Relapse may occur if maintenance Tx of stable pt is withdrawn inappropriately
3) Relapse often delayed for several weeks after cesssation of Tx
- Adipose tissue act as depot reservoir after chronic regular usage of antipsychotics until depletion.
What are some methods to overcome poor treatment adherence to antipsychotic medications?
1) IM long-acting injections of antipsychotic medications
2) Community psychiatric nurse
3) Patient & family (caregiver) education
Explain the mechanism of action of antipsychotics in general, with respect to the central dopamine system.
Intended MOA:
1) Blockade of the mesolimbic tract
- Common MOA of ALL antipsychotics
- Overactivity in mesolimbic tract is responsible for +ve symptoms of schizophrenia
Unintentded MOA resulting in adverse effects:
1) Blockade of mesocortical tract:
- Responsible for higher-order thinking & executive functions
- Hypofunction / DA blockade results in -ve symptoms
2) Blockade of nigrostriatal tract:
- Responsible for modulation of voluntary movement
- DA blockade results in extrapyramidal side effects (EPSE), such as tardive dyskinesia, akathisia & acute dystonia
3) Blockade of tuberinfundibular pathway
- Regulates prolactin secretion into blood circulation
- DA blockade causes hyperprolactinemia & thus results in gynecomastia in males OR breast swelling, pain & increased lactation in females
What are some receptor affinities of antipsychotics?
What are the clinical implications associated to these receptor affinities?
1) D2 Antagonism:
(+) Improve +ve smx
(-) EPSE, hyperprolactinemia
2) 5-HT1A agonism:
(+) Anxiolytic
3) 5-HT2A antagonism:
(+) Improve -ve smx (?), antidepressant effect (?)
4) 5-HT2C antagonism:
(-) Weight gain, increased appetite
5) H1 antagonism:
(-) Sedation, weight gain
6) alpha-1 adrenergic antagonism:
(-) Orthostatic hypotension
7) M1 antagonism:
(-) Anticholinergic SE: Blurry vision, dry mouth, constipation, urinary retention, confusion, memory dysfunction
8) hERG / Ikr antagonism:
(-) QTc interval prolongation (pro-arrhythmic)
Explain the algorithm guiding the pharmacological treatment of schizophrenia.
1) Use a SINGLE FGA or SGA (EXCEPT clozapine)
- Individualise medication selection based on physician’s assessment, past responses/failures on antipsychotics, pt needs, efficacy & side effect profiles.
2) Use another SINGLE FGA or SGA (EXCEPT clozapine) that was NOT previously tried, if there is adequate or no response.
3) If NOT responsive to at least two adequate trials (i.e. at least 2-6 weeks of optimal therapeutic doses) of antipsychotics, of which one is an SGA, use CLOZAPINE for Tx-resistant schizophrenia.
4) If still resistant to Tx w/ clozapine, add augmenting agent such as another FGA/SGA/ECT (electroconvulsive therapy) to clozapine.
- Adequate trial for clozapine requires more time (up to 3 months) to confirm therapeutic response.
- Adequate augmentation trail of up to 8-10 weeks is required if another antipsychotic is added to clozapine.
5) If pt. refused clozapine or experience intolerable side effects from clozapine, adopt last-line combination therapy of antipsychotic combination (either FGA+FGA, or FGA+SGA), or antipsychotic + either ECT or another agent (e.g. mood stabiliser)
* If adequate response AND no tolerable side effects AND adherent, continue antipsychotic Tx.
Under what condition is clozapine clinically indicated in the treatment of schizophrenia?
Treatment-resistant schizophrenia
- At least TWO adequate trials of antipsychotics, of which one is an SGA must be administered prior to starting clozapine.
- Best in reducing suicidality.
- However, routine haematological monitoring of baseline & periodic absolute neutrophil count REQUIRED when using clozapine due to risks of neutropenia, cytopenia or clozapine-induced agranulocytosis!!
