Schizophrenia

> 2 symptoms for a significant percent of time during a 1 month period (less if treated). At least one symptom must be delusions, hallucinations, or disorganized speech.

One or more areas of function (work, interpersonal relations, self-care) must be markedly below the previous level for significant portion of time as evidence by social isolation, difficulty maintaining employment or employment below educational level, impaired self-care, impaired or diminished family or social relationships.

Symtoms that are added on to a person's normal behavior

Hallucinations
Delusions
Disorganized speech
Grossly disorganized or catatonic behavior

Symtoms that reflect a decrease in normal functioning

Blunted affect: Reduction in intensity of affect (difficulty expressing emotions)
Alogia: Inability to speak
Avolition: Lack of desire or motivation to pursue reasonable goals
Anhedonia: Inability to experience pleasurable emotions
Amotivation: Inability or unwillingness to participate in normal social situations

Mood symptoms are not associated with schizophrenia

Difficulty maintaining attention
Deficits in working memory and long-term memory
Deficits in executive function

No labs show objective signs, but brain imaging including CT, MRI, and PET scans can show structural and functional changes.

Symptoms of schizophrenia for > 2 weeks, and then a major depressive or manic episode concurrent with schizophrenic symptoms. Mood episodes are present for substantial portion of illness.

BPRS Brief Psychiatric Rating Scale
PANSS Positive and Negative Syndrome Scale

exact cause of schizophrenia unknown

Risk factors include:
Peritnatal insults (hypoxia, fetal distress, influenza, famine)
Infectious and autoimmune causes
Excessive pruning of synapses because of greater complement activity (i.e. C4)
Use of cannabis, methamphetamine
Genetics, 10% risk in first-degree relatives

Negative and cognitive symptoms likely to occur

Late teens to mid-30s

gradual loss of grey matter, which may be worsened by subtance abuse

patients fluctuate between moderate and severe disability, periods of recovery may last several years

DA hyperactivity in limbic system

DA hypofunction in prefrontal cortex

current treatments only block DA, so it may worsen negative symptoms

Psychotic symptoms begin to respond within 2 weeks but may take 4-6 weeks for full effect
Agitation, aggression, and increased motor activity will begin to resolve within days

An early nonresponse (<20% reduction in PANSS or BPRS score at week 2) is highly predictive of later nonresponse, consider switching antipsychotic

First-episode psychosis: Continue antipsychotic for > 1 year after adequate symptom control to prevent relapse, 60-70% relapse rate within 1 year and 90% relapse within 2 years without maintenance treatment.
Multiple episodes: Maintain on antipsychotic for 2-5 years. If multiple prior episodes or > 2 episodes within 5 years, consider lifelong treatment.

Patients who become pregnant while taking an antipsychotic should not stop abruptly, usually continue current therapy if effective
Untreated illness may result in poorer pregnancy outcomes (i.e. low birth weight)
Breast-feeding generally not recommended (limited data)

Use the lowest effective dose
Children may be more susceptible to adverse effects
Avoid > 1 antipsychotic

SGAs
FGAs

SGAs
FGAs

Clozapine

Treatment of thought symptoms is the same as treatment of schizophrenia
Treatment of mood symptoms is the same as treatment of bipolar disorder or MDD (depending on type of schizoaffective disorder)

May be appropriate in the following scenarios:
1. > 3 failed trials of antipsychotic monotherapy
2. Cross-titration of antipsychotic medications
3. Augmentation of clozapine
4. Treatment with an antipsychotic + aripiprazole to treat hyperprolactinemia induced by the initial antipsychotic

Benzodiazepines:
Lorazepam
Diazepam
Midazolam

Antipsychotics:
Haloperidol
Chlorpromazine
Olanzapine
Loxapine Staccato

Most commonly used BZD for acute agitation (po or IM)
Rapid, complete IM absorption with duration of 8-10 hours
May cause respiratory depression, so avoid in patients with severe COPD

Onset ~30 minutes, erratic IM absorption (po >> IM)

IM or IV only, fast onset but shorter duration of sedation
Caution in pts with cirrhosis or alcohol intoxication
Higher risk of respiratory depression

Most commonly used antipsychotic, often considered med of choice
Usually administered in combo with lorazepam, diphenhydramine

Second-line due to risk of orthostasis

IM olanzapine cannot be administered with IM BZD, leads to excessive sedation and cardiorespiratory depression

Oral inhalation, restricted to REMS-certified facilities due to risk of severe bronchospasm (contraindicated in asthma and other airway diseases)

>1500 / uL
>1000 / uL

Initiate treatment
If treatment interrupted for <30 days, continue monitoring as before
If interrupted for >30 days,

Weekly from initiation to 6 months
Every 2 weeks from 6-12 months
Montly after 12 months

1000-1499 / uL

Continue recommendation

3 times per week untill ANC >1500, then return to normal monitoring

500-999 / uL

Recommend hematology consult, interrupt treatment for suspected clozapine-induced neutropenia, resume when ANC >1000 / uL

Daily until ANC >1000 / uL

<500 / uL

Recommend hematology consult, interrupt treatment for suspected clozapine-induced neutropenia, do not rechallenge unless prescriber determines benefits>risks

Daily until ANC >500 / uL, then 3x per week until patients established baseline
If rechallenged, resume treatment as if new patient