Schizophrenia treatment Flashcards
What are the major flaws of current treatments for schizophrenia?
- all current treatments were discovered by change
- make little/ no difference to cognitive symptoms
- compliance is difficult due to side effects
- Issues with pregnancy - can’t take if conceiving a new born.
What are the two types of anti-psychotics?
Typical and Atypical
What are the problems with typical anti-psychotics?
Need 60-70% block of D2 receptors to be blocked to have therapeutic effect. Very hard to get optimal efficacy for schizophrenia symptoms without experiencing motor side-effects and parkinson like symptoms. Extrapyramidal effects at >80% block.
Why do you get Extra-pyramidal motor side effects?
Blocking dopamine in the nigrostriatal pathway leads to parkinsonisms as a short term effect (tremor, muscle rigidity, loss of facial expression). Long term effects can result in Tardive Dyskinesia which is irreversible even with treatment cessation.
What are the advantages of Atypical antipsychotics?
e.g clozapine
> Ultimately, anti-psychotics with adherence have good control over +ve symptoms such as hallucinations and delusions.
> good for hallucinations and delusions but only minor improvements in cognitive deficits. Little to no effect on working memory which is extremely debilitating.
> been shown in rat models to reverse the decreased PV interneuron labelling seen in PCP treated rats - possibly indicates a regenerative effect of antipsychotics
> better extrapyramidal symptom profile as it has a low affinity for the D2 receptors in the striatum but higher binding in the cortex. More complex pharmacological profile is probably why it is working better.
> Some evidence to suggest that it is more effective in treating treatment resistant patients.
> More efficacious at treating +ve symptoms but still sub-optimal.
Side-effects associated with Atypical Anti-psychotics?
- Clozapine associated with agranulocytosis
D2 mediated side effects - block dopamine in the tuberoinfundibular pathway and therefore get prolactic release and unwanted milk production.
H1 (histamine) mediation - sedation and weight gain.
M1 (muscarinic acetylcholine mediated)- dry mouth, blurred vision, urinary retention and weight gain
alpha1 mediated - postural hypotension.
What is the usual time-course of response to anti-psychotics?
1-3 days - decreased anxiety/ agitation
1-2 weeks - improvements in socialisation and mood
3- 6 weeks - improvement in thought disorders and delusions and hallucinations.
Long-time for the onset of drugs so hard to get patients to continue with treatment whilst experiencing adverse side effects.
Outline new treatment approach targeting NMDA receptor activity
More focus on glutamatergic involvement than dopamine theory. Many drugs have been shown to work at an animal level but have been much less efficacious at
- Enhancement of NMDA activity by targeting the glycine modulatory side
- positive modulation of mGluR5 (involved in potentiation of NMDA signals)
What is the flaw of treating adults with the disease?
It is a developmental disease so likely to be much more advantageous to treat adolescents with prodromal symptoms
Existing therapies target the symptoms of schizophrenia rather than the underlying pathophysiology and treatment plans are generalised despite variability in both symptoms and treatment response.
What is nicotines association with SZ?
70-80% of patients with SZ smoke as a form of self medication as nicotine has cognitive enhancing effects.
Nicotine relases 5-HT and DA receptors
Sparked interest into treatment of schizophrenia via nicotine receptors.
Give 2 completely novel way to treat schizophrenia?
Expansion of the dopamine hypothesis has led to promising therapeutic approaches for schizophrenia. Successful novel treatments for schizophrenia will be based on a greater understanding of altered brain circuitry, the genetic underpinnings and pathophysiology of complex disease. Such developments should lead to the elucidation of biomarkers and the development of individualised treatment plans that are more targeted and treat -ve and +ve symptoms.
As of yet there have been few fundamental innovations in the treatment of schizophrenia. Current treatment limited to antipsychotics that are suboptimal and limited. Great demand for novel therapeutic approaches for schizophrenia.
- Implantation of gabaergic precursor cells (go on to become interneurons) prevents PCP induced cognitive deficits in animal models
- tDCS
- Target the PV+ interneurons - many specific peptides/ion channels on these interneurons so might be able to target these more specifically.
How can tDCS be used to treat schizophrenia?
Use of cathodal to diminish activity in the left temporoparietal cortex (TPC) to reduce auditory hallucinations, a frequent positive symptom, potentially relevant target of stimulation. For improvement in -ve symptoms anodal stimulation of the Left DLPFC
