Schizophrenia

Disease Review And Treatment Update

Edward Moldenhauer, MS, RPh LCDR, MSC, USN

Schizophrenia
Goal:
To familiarize the practitioner with schizophrenia and current treatment options for the disease

Schizophrenia
Objectives:
- Describe how schizophrenia is diagnosed - Describe the symptoms of schizophrenia - Identify the common side effects of schizophrenia medications - Describe adjunct medication treatment options for schizophrenia - Compare schizophrenia medications relating to dosing, special patient populations, side effects, interactions and precautions

Schizophrenia
True stories:
I thought that I had been shot in the head to remove a blood clot. Then, I actually felt my brain crack open, masses of blood came out of one of my ears and a small trickle from the other. Later that night, I thought that the devil was after me, I saw him come through one of the speakers of my stereo system. I was also probably hearing voices, but they were mixed in with the radio music and DJs.

Schizophrenia
True stories:
I had one particular friend. I called him the Controller, only I could see him and hear him, but no one else could. He would punish me if I did something he didn't like. He spent a lot of time yelling at me and making me feel wicked. I didn't know how to stop him from screaming at me and ruling my existence. It got to the point where I couldn't decipher reality from what the Controller was screaming.

Schizophrenia
True stories:
Louis Wain, a prominent British artist of the early 1900's, was diagnosed with schizophrenia. He was under psychiatric care but lived at home surrounded by his cats. Over a period of years he painted their portraits, which are in a way self-portraits, revealing the tragic odyssey of his feelings.

Schizophrenia
True stories:
John Nash, noble prize winning mathematician, was virtually incapacitated by paranoid schizophrenia during the prime of his genius. Referred to as Princetons "Phantom of Fine Hall, he was a ghostly, silent figure shuffling around wearing purple sneakers and occasionally writing treatises on blackboards. He was immortalized in 2002 Academy Award winning film, A Beautiful Mind.

Schizophrenia
Description:
- a psychotic disorder characterized by a loss of contact with the environment, by noticeable deterioration in the level of functioning in everyday life, and by the disintegration of personality expressed as disorder of feeling, thought, and conduct
Merriam-Webster Dictionary

Schizophrenia
Description: - chronic, severe, disabling
-- one of the most disabling and emotionally devastating illnesses - first identified in 1911 - NOT split personality - linked to anatomical abnormalities - a neurodevelopmental disorder of excessive dopamine levels

Schizophrenia
Demographics: - risk factors;
-- genetic -- perinatal - gender/age distribution -- men & women equally prone -- males; late teens/early 20s -- women; late 20s to early 30s - no known racial differentiation - most patients are smokers

Schizophrenia
Childhood Schizophrenia:
- rare in US (0.01% or 1 in 10,000) - recently separated from autism - occurrence rates increase as child approaches adulthood - suicide mortality rate: 5-11% - child may exhibit a failure to meet expected life milestones rather than deterioration in functioning

Schizophrenia
DSM-IV Criteria:
- at least 2 characteristic symptoms present for most of a 1-month period over a 6-month period:

Delusions Hallucinations Disorganized speech Catatonia / disorganized behavior Negative symptoms

Schizophrenia
Symptoms:
- insidious onset in 50% of patients - characterized by a group of distinctive & predictable symptoms

- positive symptoms
(grossly abnormal behavior) -- behavior that is there that shouldnt be

- deficit or negative symptoms

(absence of normal behavior) -- behavior that is not there that should

Schizophrenia
Positive Symptoms:
- thought disorder -- diminished ability to think clearly and logically -- manifested by disconnected and nonsensical language -- incapable of participating in conversation

Schizophrenia
Positive Symptoms (cont):
- delusions -- false yet strongly held belief resulting from an inability to separate the real from unreal -- paranoid delusions: belief that they are being conspired against -- broadcasting: belief that thoughts can be heard by others

Schizophrenia
Positive Symptoms (cont):
- hallucinations -- heard, seen, or even felt -- most often they take the form of voices heard only by the patient -- may describe the person's actions, warn of danger or direct actions -- at times, several voices may be carrying on a conversation

Schizophrenia
Deficit or Negative Symptoms:
- the absence of normal behavior - flat or blunted affect (i.e. lack of emotional expression) - apathy - social withdrawal

Schizophrenia
Diagnostic Parameters:
- Cross-sectional -- current clinical status - Longitudinal -- frequency -- severity -- treatments -- consequences of past episodes

Schizophrenia
Diagnostic Tools:
- Structured Clinical Interview for DSM-IV (SCID) -- gold standard -- admin by psych professional -- takes 1-2 hours to administer - Teaching Interview for Psychiatric Students (TIPS) -- shorter than the SCID -- guide for routine, brief clinical evals

Schizophrenia
Diagnostic Tools:
- Positive and Negative Syndrome Scale (PANSS) -- structured clinical interview tool -- 30-40 minute formalized interview -- 30 questions on a 7-point scale -- separates out nine different clinical dimensions - Brief Psychiatric Rating Scale (BPRS) -- evaluates psychotic symptoms -- numerically scales symptoms

Schizophrenia
Differential Diagnosis:
- other psychological disorders -- bipolar affective disorder -- delusional disorder -- schizotypal personality disorder - other medical illnesses -- brain tumor, intracranial bleeding -- head trauma -- systemic lupus erythematosus -- Huntington disease

Schizophrenia
Differential Diagnosis:
- metabolic disorders -- Wilsons disease -- porphyria -- hypoxemia -- electrolyte / vitamin imbalances

Schizophrenia
Differential Diagnosis:
- endocrine disorders -- hypo- or hyperthyroid -- hypo- or hyperadrenalism -- hypo- or hyperparathyroidism

Schizophrenia
Differential Diagnosis:
- infectious diseases -- neurosyphilis -- HIV-1 -- cerebral abscesses -- Creutzfeldt-Jakob disease

Schizophrenia
Differential Diagnosis:
- miscellaneous -- multiple sclerosis -- heavy metal poisoning -- seizure disorder -- substance abuse

Schizophrenia
Differential Diagnosis:
- medications corticosteroids (psychosis/mania) levodopa (hallucinations/insomnia) antidepressants (mania) interferon-alpha (depression) beta-blockers (depression)

Schizophrenia
Disease Course:
- initial signs may appear as weird changes in normal behavior - acute -- onset of severe psychotic sx - psychosis -- state of mental impairment marked by hallucinations and/or delusions

Schizophrenia
Disease Severity:
- single -- only one episode - mild/moderate -- many episodes over lifetime with relatively normal during interims - chronic -- continuous or recurring -- often do not fully recover -- typically require long-term tx

Schizophrenia
Chronic Disease Treatment:
- some patients completely recover - many must be institutionalized - medication treatment -- 70% of patients respond well -- 15% moderately improve but still require support -- 15% have no response

Schizophrenia
Disease Treatment:
- supportive therapy -- social work, family counseling -- vocational rehabilitation - hospitalization -- brief in-patient to stabilize - out-patient care -- alcohol and drug abuse -- depression -- medication non-compliance

Schizophrenia
Disease Treatment Phases:
- acute phase -- alleviate/reduce acute symptoms -- assessment -- treatment setting -- psychiatric management -- initiate medication

Schizophrenia
Disease Treatment Phases:
- stabilization phase -- minimize stress and relapse - stable/maintenance phase -- assessment -- psychiatric management and specific psychosocial treatments -- monitoring medications -- early intervention

Schizophrenia
Medication Adherence/Relapse:
- up to 75% of patients don't take their medication regularly or stop treatment altogether - ~80% relapse within one year if medications are stopped - only 20% relapse if continually treated

Schizophrenia
Medication Classes:
- classic antipsychotics -- haloperidol (Haldol) -- droperidol (Inapsine) -- fluphenazine (Prolixin) -- thioridazine (Mellaril) -- chlorpromazine (Thorazine) - a.k.a.; "neuroleptics, due to potential for inducing neurological side effects

Schizophrenia
Medication Classes:
- atypical antipsychotics -- Clozapine (Clozaril) -- Risperidone (Risperdal) -- Olanzapine (Zyprexa) -- Quetiapine (Seroquel) -- Ziprasidone (Geodon) -- Aripiprazole (Abilify) - a.k.a.; SDAs -- serotonin-dopamine antagonists -- pleiotropic pharmacology

Schizophrenia
Medication Classes:
- therapy adjuncts -- pimozide (Orap) -- divalproex (Depakote) -- carbamazepine (Tegretol) -- lithium -- anticholinergics -- benzodiazepines (BZDs) -- antidepressants -- ECT

Schizophrenia
Classical Antipsychotic Side Effects: (a.k.a.; EPS: Extrapyramidal Side Effect)
- akathisia (restless leg) - dystonia - hyperprolactinemia - akinesia & Parkinsonism-like sx - weight gain - anticholinergic adverse effects

Schizophrenia
Classical Antipsychotic Side Effects: (a.k.a.; EPS: Extrapyramidal Side Effect)
- Neuroleptic Malignant Syndrome (NMS) -- hyperthermia -- muscular rigidity -- altered mental state -- autonomic instability

Schizophrenia
Classical Antipsychotic Side Effects: (a.k.a.; EPS: Extrapyramidal Side Effect)
- Tardive Dyskinesia (TD) -- high incidence in elderly (~70%) -- involuntary and repetitive (not rhythmic) mvt of mouth and face -- rocking back & forth or tap feet -- diaphragmatic dyskinesia exists, -- risk factors: age, female, lower IQ, negative symptoms

Schizophrenia
haloperidol (Haldol):
- DOC for acute psychosis
(when no contraindications exist)

- dopamine (D2) antagonist - high potential for EPS/dystonia - precautions

-- monitor development of TD -- if IV/IM, monitor for hypotension -- caution in diagnosed CNS depression, cardiac disease, history of seizures -- significant in body temp may indicate intolerance

Schizophrenia
clozapine (Clozaril):
- adrenergic, cholinergic, histaminic and serotonin receptor antagonist - precautions
-- do not D/C aburptly -- requirement to perform WBC count -- hypotension, myoclonic jerks, seizures -- urinary incontinence, constipation

- requires National Registry registration

Schizophrenia
clozapine (Clozaril):

www. clozapineregistry.com

Schizophrenia
risperidone (Risperdal):
- dopamine & serotonin receptor antagonist - precautions
-- EPS, NMS, hyperprolactinemia, hypotension, tachycardia, arrhythmias -- cerebrovascular warning of stroke in elderly patients with dementia -- can lengthen QT interval

- availability
-- oral tablets, soln, & distinegrating tabs

Schizophrenia
olanzapine (Zyprexa):
- dopamine, serotonin and muscarinic receptor antagonist - precautions
-- glaucoma, vascular disease, BPH, seizures, hypovolemia, dehydration -- may lead to weight gain

- availability
-- oral tablets, disintegrating tablets

Schizophrenia
quetiapine (Seroquel):
- dopamine and serotonin receptor antagonist - precautions
-- may induce orthostatic hypotension associated with dizziness, tachycardia, and syncope -- NMS

- availability
-- oral tablets

Schizophrenia
ziprasidone (Geodon):
- dopamine and serotonin receptor antagonist - injectable used for acutely agitated pt - precautions
-- prolongs QT/QTc (caution in patients with known risk factors) -- caution in seizure disorders -- may cause hypotension, EPS, somnolence

- availability
-- oral capsules and injection

Schizophrenia
aripiprazole (Abilify):
- MOA is unknown, hypothesized to work differently meds - antagonizes serotonin (5HT2A) - partial dopamine (D2) and serotonin (5HT1A) agonist - precautions:
-- headache, anxiety, somnolence, and insomnia

- availability
-- oral tablets

Schizophrenia
- Debilitating to patient, family, society - Severe personality changes - Linked to neurochemical abnormalities - Positive and Negative Symptoms - Differential diagnosis - Treatment options - classic and atypical antipsychotics - side effects and precautions

Schizophrenia