10 Schizophrenia and psychosis Flashcards
Schizophrenia Diagnostic criteria
Patient has social/occupational dysfunction for 6 months or greater from
Two of:
*Delusions
*Hallucinations
*Disorganized speech
*Disorganized or catatonic behavior
*Negative symptoms: alogia, no drive, flat affect, ahedonia, anergia, cognative symptoms
- ** If more than one voices conversing in head, or if running commentary on behavior or thoughts this is schizo regardless of other symptoms***
- **Not explained by MDD, Bipolar : Schizoaffective disorder, substances, autism, developmental delay.
Schizophrenia- overview and epidemiology
- Split among affect, thought, emotion, and behavior.
- Associations brakdown, Affect incongruent, Autism- ego boundries breakdown, Ambivalence
- 1% prevalence
- 2.5% of total healthcare expenses in US
- generally late teen insidious onset
Schizophrenia Symptom classifications
Positive: delusions, hallucinations, behavioral disturbance
Negative: Social isolation, withdrawl, poor grooming, anergy, ahedonia, blunted affect
Cognative: Impaired abstract thinking, impaired problem solving, disturbed memory
Schizophrenia etiology
DOPAMINE-MESOLIMBIC HYPERACTIVITY, MESOCORTICAL HYPOACTIVITY
- genetics?
- Anatomic- enlarged lateral ventricles, sulcal enlargement
- Physiologc- Decreased dorsolateral prefrontal cortex activation, maybe thalamus and cerebellum
- Biochemical- D2 blockers work
Schizophrenia treatment
Dopamine: serotonin antagonists
Olanzapine, risperidone, quietapne
Dopamine antagonists: Halperidol, chlorpromazine, fluphenazine
SE: Dystonia, akasthisia (restlessness), Tardive dyskinesia (lipsmacking)
Psychosocial: Housing, case management, psychotherapy, vocational training.
Schzophrenia: Psychological treatment
- Assertive community treatment
- Biological rhythm adherence, medication adherence, aoid abuse substances
- Social Skill training
- Family therapy: Decrease displays of emotion
Schizophrenia prognosis
Relapses common-
Positive symptoms wane
Negative symptoms wax
Patients with outspoken family members do poorly
20-30% normal life, 20-30% moderate symptoms, 40-60 impaired
Schizophreniform disorder
<6 months
Brief psychotic disorder
1 day to 1 month
Schizoaffective Disorder
Concurrent mood disorder
Delusional disorder
No functional impairment except delusions
Dopamine pathways
*Mesolimbic- Ventral tegmentum to limbic lobe- Memory, arousal, stimulus processing, locomotor activity, motivational behavior - DA upregulated- positive symptoms
*Mesocortical- Ventral tegmentum to neocortex- cognition, communication, social activity- DA decreased- negative symptoms
*Niagrostriatal- substatia niagra to basal ganglia and extrapyramidal system- pharmacologic D2 Blockade downregulates EPS-> parkinsonism
*Tuberoinfandibular- Hypothalamus to pituitary- Blockade causes increased prolactin release
Tuberoinfandibular
Post synaptic dopamine receptors
D2R- Downregulated cAMP but upregulates IP3
D1R- Upregulates cAMP
Presynaptic dopamine receptor
D2 like- downregulates presynaptic cAMP and prevents vesicular fusing
Atypical Antipsychotics
Clozapine, risperidone, olanzapine, quietapine
DA blockade
5HT2 blockade in forebrain
Pharmacokinetics of antipsychotics
Variable oral absorption Lipid soluble Protein binding Large volume of distribution Complex metabolism
Antipsychotics
- Best for treatment of positive symptoms
- Work less well for negatives (though atypicals help these)
- Classics cause sedation
- Extrapyramidal effects- dystonia(1-5 days), parkinsonism(1wk-1month), akasthisia(1wk-2months), Tardive dyskenesia (months to yrs)
Antipsychotic SE
- Variable anticholinergic side efects (dry as a bone, blind as a bat, hot as a hare)
- orthostatic
- Neuroendocrine effects
- allergic, liver, blood effects
- THIORIDAZINE CARDIAC EFFECTS
- Phenothiazines- Seizure threshold
- weight gain (atypicals)
Neuroepileptic malgnant syndrome
- Potentially lethal
- Hypodopaminergic side effect
- Hyperthermia
- parkinson-like symptoms
- mutism and death
Tx-
Cooling, hydration, bromocriptine, dantrolene
Phenothiazines
Original typicals
- Fluphenazine, Perphenazine, Prochloroperazine, Trifluorperazine
- Piperazines
- Very potent
- Less sedative
- Highly extrapyramidal
- Thioridazine, Mesoridazine
- Low potency
- sedative
- anticholinergic
- Chlorpromazine, Triflupromazine
- medium potency, sedatie, anticholinergic
Chlorprothixene, Thiothixene
like phenothiazines
Haloperidol
Acts similar to Piperazines
- high potency, sedative, extrapyramidal reactions
Pimozide
- Neuroleptic
- Many side effects
- Tourettes treatment
*Clozapine
- D4- 5HT2 blocker
- Improves refractory positive smptoms as well as negatives
- Antimuscarinic
- SEVERE SEIZURE THRESHOLD LOWERING
- AGRANULOCYTOSIS
- DECREASES SUICIDE
Olanzapine
- D1, D2, 5HT2 antagonist
- Rare extrapyramidal symptoms, no siezures, no agranulocytosis
- WEIGHT GAIN AND DIABETES
- reports of abuse
Risperidone
- D2 5HT2 antagonist
- Reduction in negative symptoms
- Less seizure and anti-muscarinic effects
- IM available
- paliperidone is active metabolite
Quietapine
- 5HT2 and D2 antagonist
- similar to clozapine
- Good for negative symptoms
- some weight gain
- Shorter half life
- Approved for depression augmentation
Ziprasidone
- 5HT2 and D2 antagonist- may have 5HT1a agonist effect (anxiolytic)
- No weight gain
Aripirazole
- Partial D2 agonist, 5ht2 antagonist
- less weight gain
- Depression augmentation
Lithium
- MANIA/BIPOLAR, UNIPOLAR DEPRESSION, SCHIZOAFFECTIVE, CLUSTER HA
- Antipsychotic- blocks IP2 recycling to IP1
- blocks manic behavior
- No effect on normals
- Narrow therapeutic window
- 12-24 hour half life
- free cation is plasma
- 95% urine elimination
- Interactions with high sodium, ACEi and ANGII
Lithium SE
Fatigue/muscular weakness
Tremor (treat with B blockers)
GI symptoms
Inpaired consciousness coma and death at 2-3X
AEDS for mania
Carbemazepine
Valproic acid/Divalproex
Lamotrigrine and topirimate
olanzaine/fluoxetine (symbyax- bipolar, refractory MDD
