Schizophrenia 2 Flashcards
Goals of Therapy
Acute (7 days)
* Initial
management of
acute psychosis
* ↓risk of harm to
self and others
* ↓agitation,
hostility
2-3 weeks
* ↑socialization
* Improvement in
self-care, mood
* ↓severity of
positive
symptoms
2-3 months
* Improvement in
thought disorder
* ↓ severity of
symptoms
* Minimize
medication side
effects
* Provide
medication
education
* Improve social
functioning
Maintenance
* Improve social
and
occupational
functioning
* Promote
compliance to
medications
* Reduce and
manage
medication side
effects
* Minimize long
term health risks
* Prevent Relapse
Non-Pharmacological Treatment
- Psychological therapy
- Psychosocial rehabilitation
- Case management
- Basic living skills
- Social skills training
- Financial support e.g., Alberta Works or AISH
- Supportive housing
- Psychoeducation
- Family therapy
- Multidisciplinary healthcare teams
- Assertive Community Treatment Teams (ACTT)
- multi-disciplinary teams that provide comprehensive services to lower functioning patients. This may include medication management, case management, help with daily living skills, supportive housing, supported employment. And these can help with that kind of like psycho social approach to treatment while also providing help with medication management.
- Electroconvulsive Therapy (ECT)
- Evidence in treatment-resistant cases
Treating Schizophrenia
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this is the first episode. They have no impairment. They can if it’s treated, return to their baseline. Once they’ve had several episodes, they might still continue to have no or minimal impairment. Some patients might have impairment after the first episode. And they might never returned to their baseline
this can also happen with several episodes where their baseline level of functioning is just significantly impaired. And using medications early on and making sure that they’re effective, appropriately dosed can help reduce that impairment that patients experience from relapse
Antipsychotic Therapy
- Anti-psychotic = neuroleptic
- Indicated for most causes of psychosis, extensively studied for
schizophrenia - Well-established evidence for reducing positive symptoms and
improving outcomes - Efficacy for management of negative symptoms is less clear
Divided into two or three categories:
* Typical or 1st generation antipsychotics
* Increased D2
receptor occupancy
* Varying levels of potency (related to D2
-receptor antagonism)
* Atypical or 2nd (+/- 3
rd generation) antipsychotics
* Lower or transient D2 occupancy (more time off of D2
receptor)
* 5-HT2A receptor antagonism
How to decide which antipsychotic to use?
they still affect dopamine, but they might not just like they’re not binding to it for a prolonged period. They spend some time off over the receptor. This is thought to reduce the side effects, the movement related side-effects or that prolactin side effects that are related to dopamine. And then they also have serotonin receptor antagonism
Treatment Selection
Clinical Antipsychotic Trials of Intervention Effectiveness (2005)
“Among patients with schizophrenia, how do the second-generation
antipsychotic medications such as olanzapine, quetiapine, risperidone and
ziprasidone compare to first-generation antipsychotic medications such as
perphenazine in terms of relative effectiveness?”
Design:
* Multicenter, double-blind, parallel-group, randomized, controlled trial
* N=1432
* Olanzapine vs. quetiapine vs. risperidone vs. perphenazine vs. ziprasidone
* Compared long term effectiveness and safety
* Primary outcome: Discontinuation of treatment for any cause
Primary outcome:
* Discontinuation for any cause
* Only 26% of patients completed 18 months of the study drug to which they were randomized
* Patients in the olanzapine group had the lowest rate of treatment discontinuation
* Time to discontinuation: Olanzapine had longest time to discontinuation
* NS vs perphenazine and ziprasidone)
Secondary outcomes:
* Discontinuation due to lack of efficacy: olanzapine < ziprasidone < perphenazine < risperidone <
quetiapine
* Hospitalization for exacerbation of schizophrenia: olanzapine < risperidone < perphenazine <
ziprasidone < quetiapine (p<0.001)
Adverse Events:
* Olanzapine: Associated with greater weight gain, hyperlipidemia, and hyperglycemia
* Ziprasidone: Associated with weight loss and improvement in lipids and in blood glucose.
- Only a minority of patients remained on their assigned treatment
- No one antipsychotic was demonstrated to have statistically significant
superior efficacy - Selection of antipsychotic therapy must involve a risk/benefit analysis
comparing effectiveness and safety: - Among patients with schizophrenia, patients receiving olanzapine experienced
a longer time to discontinuation compared with the other antipsychotic
medications, but they experienced greater weight gain, hyperglycemia and
hyperlipidemia. - Efficacy of FGAs is comparable to SGAs:
- Perphenazine generally performed as well as the newer medications. The older
medication was as well tolerated as the newer drugs and was as effective as
three of the newer medications.
Selecting an Antipsychotic: If they’re all equal …
then what?
fairly accurate to clinical practice on patients do our non-compliance to treatment or discontinuation is happens for several reasons. And while therapy with olanzapine might seem to be more effective, the marginal benefits might be diminished in the context of the adverse effect profile.
Patient-specific considerations
* Medical Comorbidities
* Metabolic
* Cardiovascular
* Psychiatric Comorbidities
* Age
* Children/youth
* Older adults
* Past medication trials (if
applicable)
Medication considerations
* Dosing e.g., once, twice, three
times daily
* Availability in long-acting
injectable format
* Side effect profile
Cardiovascular Risk
- Patients with or at risk of metabolic syndrome e.g., pre-existing
diabetes, obesity, hypertension, dyslipidemia tip scale away from
antipsychotics with higher metabolic risk e.g., olanzapine, quetiapine,
risperidone - Risk for QT prolongation: avoid medications with greater association
with long-QT syndrome e.g., ziprasidone, quetiapine, chlorpromazine
Psychiatric Comorbidities
- Insomnia: selection of agent with sedating properties e.g., quetiapine,
olanzapine, risperidone, etc.. - Affective symptoms:
- Mania: selection of agent with evidence in treating mania e.g., risperidone,
paliperidone, aripiprazole, quetiapine, etc.. - Depression: selection of agent with evidence in treating managing depression e.g.,
risperidone, quetiapine, aripiprazole are all first-line augmenting agents, quetiapine
is second-line monotherapy - Anxiety disorders:
- E.g., GAD: quetiapine, aripiprazole, risperidone can be used as augmenting agents for
GAD, quetiapine can be used as monotherapy in some cases - Obsessive-Compulsive Disorder (OCD): Second-generation antipsychotics
can exacerbate or result in “de novo” OCD symptoms
Quetiapine: manic symptoms, it can also be used to treat anxiety. It’s one of the first-line augmenting agents for depression and anxiety and can also be used as monotherapy for, as monotherapy for generalized anxiety.
Older Adults
- Older adults (>70y) are more susceptible to antipsychotic side effects
- Particular caution paid to anticholinergic side effects e.g., dry mouth,
blurry vision, urinary hesitancy, constipation, and cognitive side
effects - Also consider risk of orthostatic hypotension
- Increased risk of falls
- Selection of agents with lower alpha-antagonist activity
First-Episode Psychosis
- Many things unclear in first-episode psychosis
- Primary psychotic disorder
- Underlying medical condition
- Substance use
- No placebo-controlled trials in this population (unethical)
- In most cases commence treatment with antipsychotic therapy as
early as possible - Meta-analyses show that shorter duration of untreated psychosis better
outcomes
when we see a patient with first episode psychosis, they have likely not yet been diagnosed with schizophrenia because per the diagnostic criteria, a degree of chronicity is needed for the schizophrenia diagnosis to be made.
would still want to initiate treatment with antipsychotics to reduce any risk to the patient
Acute Management of Psychosis
- Initiate symptomatic treatment with antipsychotic
- SGA preferred first-line
- Common antipsychotics used if severely agitated/psychotic:
- Olanzapine 2.5-10mg PO/IM
- Loxapine 25-50mg PO
- Haloperidol 5mg PO/IM
- +/- lorazepam 1-2mg PO/IM
- SEVERE agitation (harm to self/others): zuclopenthixol acetate
(Clopixol Accuphase) 50-150mg IM (72h duration)
After initial agitation has been managed)
* Preferred for SGA/TGA as first-line agent (↓risk EPS)
* Start with low dose, titrate to effect/tolerance
* Can increase dose q2-3d in hospital
* Ambulatory setting: usually q1wk
only exception that might be made to starting low with an oral, oral anti-psychotic is if a patient just refuses to take any treatment with oral medications. In this case, they might be deemed as being incapable and an injection would be given
his is never the preference in any case because once you administer an injection along acting injection specifically, it’s in their system for weeks, maybe months. And if they’re having an adverse reaction, There’s not a ton you can do about it.
Stabilization/Maintenance
- Monitoring:
- Positive symptoms respond faster than others
- Response expected within 4 weeks, up to 12 weeks for full response
- Negative symptoms: up to 16 weeks
- Cognitive symptoms: up to 16 weeks
- Compliance:
- Discontinuation of antipsychotic medication increases risk of relapse
- Consider transitioning to long-acting (depot) injection
Negative symptoms and cognitive symptoms take longer and they might be more resistant to treatment, so they might not improve as markedly.
Long-Acting Injections
- Data from RCTs and meta-analyses have demonstrated advantages
over PO dosage forms - More convenient, improves compliance, prevent psychiatric hospitalization,
reduce relapse rates - Does not ensure adherence BUT ensures monitoring/awareness of adherence
- Only certain antipsychotics come in LAI form
- 2
nd generation: paliperidone, risperidone, aripiprazole - 1st generation: haloperidol, zuclopenthixol, flupentixol
- Not recommended for antipsychotic-naïve
- Always test tolerance with PO doses
while using a long-acting cannot ensure compliance. It will allow for assessment of their adherence because the question that was sent to administer the long-acting injection will be aware that it was not given in patients that are on treatment orders. They might be detained in order to administer this, which is something that is ethically unclear.
It’s not recommended to administer them in patients that are anti-psychotic, naive, that have never tried any anti-psychotic again, because once it’s in their system, you can’t really get it out.
Assessing Efficacy
- Adequate treatment trial:
- Therapeutic dose
- Minimum of 4-6 weeks
- Confirmed compliance
- At 4 weeks:
- No response consider changing medication
- Partial response optimize dose, reassess at 8 weeks
LAIs: - Therapeutic effect and attainment of steady-state are all delayed with LAI
- Allow for attainment of peak plasma levels
- For most LAIs, plasma levels increase over several weeks to months without increase
of dose - Accumulation
Assessing Response to Treatment
read
- Symptoms: Absolute symptoms vs. symptom change
- Absolute symptoms: Treatment response defined as having no more than mild
symptoms - Symptom change: Evaluation of treatment response relative to a baseline.
- A change of 20% is the minimum that can be routinely detected clinically. Therefore
reduction less than 20% will correspond to a clinically insignificant reduction in symptoms. - Use a validated rating scale, e.g.:
- Positive and Negative Syndrome Scale (PANSS)
- Brief Psychiatric Rating Scale (BPRS)
- Scale for the Assessment of Negative Symptoms (SANS)
- Scale for the assessment of Positive Symptoms (SAPS)
*Administered by a psychiatrist who is trained to do so
