Antipsychotics Perceptual distortion (hallucinations)

- AKA neuroleptics, major tranquilizers - Sensory perceptions not directly attributable to

- “Neuroleptics” = cause movement disorders environmental stimuli (appear real to the schizophrenic):
- “Major tranquilizers” = reduce anxiety, fear - Auditory (hearing)
- Visual (seeing)
Psychosis - Olfactory (smelling)
- Symptoms of delusions, hallucinations, and disorders of - Tactile (feelings)
thought; increased dopamine levels - Gustatory (tasting)

Schizophrenia Greatest distress - voices are dominant and insulting; lacks

- pattern of social and occupational deterioration, at least 6 communication with the voices
months
- -1% of population, inheritable Coping strategies
- heterogeneous syndrome of - Distraction - Selective listening
- Disorganized and bizarre thoughts + - Ignoring - Setting limits
- Delusions +
- Hallucinations + ★ Negative symptoms
- Inappropriate affect - Present in a normal, missing in the schizophrenic
- Impaired social functioning - Associated with inferior premorbid social functioning
- Flat affect - little or no emotion
COURSE OF SCHIZOPHRENIA - Alogia - poverty of speech
★ Prodromal phase - onset and buildup of symptoms - Avolition - inability to take action
★ Active phase - full-blown: severe disturbances in thinking, - May indicate irreversible neuronal loss in a
deterioration in social relationships, and flat or inappropriate affect structurally abnormal brain
★ Residual phase - Symptoms no longer prominent - Asociality: Inability to form relationships
- Anhedonia: Inability to feel pleasure
Complete recovery is rare, but schizophrenics can lead
productive lives ★ DISORGANIZED SYMPTOMS
- Disorganized speech (Formal thought disorder)
SYMPTOMS OF SCHIZOPHRENIA - Incoherence - Inability to organize ideas
★ Characteristic symptoms - Loose associations (derailment) - Rambles, difficulty
- 2 or more, at least 1-month period sticking to one topic
- Delusions - Disorganized Behavior - Odd or peculiar behavior;
- Hallucinations Silliness, agitation, unusual dress
- Disorganized speech
- Grossly disorganized or catatonic behavior ★ OTHER SYMPTOMS
Negative symptoms - Catatonia
- Motor abnormalities
★ Positive symptoms - Repetitive, complex gestures
- Not present in the normal, present in schizophrenic - Usually of the fingers or hands
- Hallucinations - perceptual experiences that do - Excitable, wild flailing of limbs
not have a basis in reality. Auditory - Catatonic Immobility
- Delusions - false beliefs - Maintain unusual posture for long time
- Distortions or excesses of normal functioning - Waxy Flexibility
- Limbs can be manipulated and posed by another
KINDS(?) OF DELUSIONS person
- Delusions of control – trying to control you - Inappropriate Affect
- Delusions of thought broadcasting - can hear your - Emotional responses inconsistent with situation
thoughts
- Delusions of persecution - will hurt you
- Delusions of reference – center of attention
- Thought withdrawal – thoughts are being removed
- Capgras’s syndrome - there’s a “double” of you who may
replace or coexist with you
*NRL - neuroleptic
**DO - disorder
TYPES OF SCHIZOPHRENIA SEROTONIN HYPOTHESIS
★ Paranoid Schizophrenia - Responsible for causing hallucinations
- One or more systematized delusions or auditory - 5HT2 activation in brain can cause hallucination
hallucinations and the absence of such symptoms as - Related to LSD and Mescaline and other drugs activates
disorganized speech and behavior or flat affect serotonin 2 receptor
- mostly positive symptoms - Excess
- Responds more readily to medication
- Most common symptom: Delusions of persecution GLUTAMATERGIC DYSFUNCTION
- PHENCYCLIDINE & KETAMINE
★ Disorganized Schizophrenia - NMDA antagonist
- Formerly hebephrenic schizophrenia - Produce “schizophrenia- like” symptoms
- Disorganized behaviors manifested by disorganized speech - Ketamine is a general anesthetic which blocks NMDA
and behavior, and flat or grossly inappropriate affect - Glutamate has many receptor which can bind to NMDA,
- Delusions and hallucinations are less organized glutamate receptors and AMPA
- Speech may become incoherent and the person may - Ampakines - drugs that potentiate currents mediated by
invent new words (neologisms) AMPA type glutamate receptors; neuroprotective

★ Catatonic Schizophrenia DOPAMINE HYPOTHESIS

- significant disturbance of motor activity - Excessive dopamine in mesolimbic system
- Motoric immobility or stupor (withdrawn - Homovanillic acid (HVA) - metabolite of Dopamine
catatonia; little or no motor activity)
- Excessive purposeless motor activity (excited
catatonia)
- Extreme negativism or physical resistance
- Peculiar voluntary movements
- Echolalia or echopraxia (gaya-gaya, puto maya)
- Behavior may become dangerous/violent

★ Undifferentiated Schizophrenia
- shows prominent psychotic symptoms not meeting criteria
for paranoid, disorganized, or catatonic schizophrenia
(Doesn’t fit into any other category)
ETIOLOGY OF SCHIZOPHRENIA
★ Residual Schizophrenia - Biological
- At least one previous schizophrenic episode but current - Genetic, brain-structure, & biochemical explanations
absence of prominent psychotic features
PHYSIOLOGICAL FACTORS IN SCHIZOPHRENIA
PSYCHOTIC DISORDERS ONCE CONSIDERED SCHIZOPHRENIA - High Neurological Activity
★ Brief psychotic DO** - at least 1 day but < 1month - PET scans show higher levels of activity in the prefrontal
★ Schizophreniform DO - at least 1month but < 6 months cortex and temporal cortex
- Differences in cerebral glucose metabolism
OTHER PSYCHOTIC DISORDERS
★ Delusional disorder - Holding nonbizarre beliefs lasting at least 1 PROBLEMS WITH BRAIN DEVELOPMENT AND ACTIVITY
month; except for the delusion the behavior is not odd - Reversed hemispheric dominance
- Common themes: grandiosity, jealousy, persecution, and - Left hemisphere didn’t develop and become dominant
somatic complaints - Failure of neural migration
★ Shared psychotic disorder - A person with a close relationship to - Movement of neurons to the gray matter is retarded
an individual with delusional/psychotic believes comes to accept - Cortical atrophy
those beliefs - Prefrontal cortex – smaller, less active, and decreasing in
- Folie a deux (Madness shared by two) size at a faster rate (hypofrontality)
- Temporal cortex - smaller and less active
Pathophysiology - Subcortical atrophy
➔ NEUROTRANSMITTER CHANGES - Enlarged ventricles
- Dopamine, Glutamate, Serotonin - Smaller hippocampus (esp. for negative)
*NRL - neuroleptic
**DO - disorder
 - Thalamus is smaller and less active Neuropsychiatric Indications
- Smaller amygdala - Antiemetic ( Prochlorperazine, Benzquinamide)
- Antihistamines (Phenothiazines)
WHO IS AT RISK? - Preoperative Sedatives (Promethazine)
- Predisposing factors - Neuroleptanesthesia (Droperidol +Fentanyl + Nitrous
- Season of birth Oxide)
- Pregnancy and birth complications - Droperidol and Fentanyl = Neurolepanalgesia
- Genetic background Haloperidol, pimozide - off-label Tourette syndrome
- Precipitating factors Aripiprazole - Asperger's syndrome
- Stress Chlorpromazine – for intractable hiccups
- Substance of Abuse Promethazine – antipruritic

MANAGEMENT OF SCHIZOPHRENIA (nonpharmacologic) ADVERSE EFFECTS

★ Psychosocial Therapy
- Practical advice, getting in touch, understanding
- Most important quality of therapist: Friendship
★ Institutional Approaches
- Social learning programs: Appropriate self-care,
conversational skills, role skills
- Undesirable behaviors are decreased through
reinforcement and modeling TYPICAL = dopa only, 1st gen, positive
★ Cognitive-Behavioral Therapy ATYPICAL = dopa & sero, 2nd gen
- Work at reducing frequency and severity of positive and
negative symptoms
- Enhance coping skills
- Weaken beliefs
- Challenge false beliefs
- Social skills training

★ Family Communication And Education

- Normalize family experience
- Educate family members
- Develop problem solving & stress management skills
- Learn to cope with symptoms
- Recognize early signs of relapse
- Create supportive family environment
- Understand/meet needs of all family members

Treatment of Schizophrenia (pharmacologic)

- Antipsychotic medication
- Neuroleptics – used interchangeably that treats
schizophrenia

RESERPINE AND CHLORPROMAZINE

- First drugs found to be useful in schizophrenia
- Reserpine – storage inhibitor; A/E: depression

USES OF NEUROLEPTICS
Psychiatric Indications
- Schizophrenia, Mania, and Delusional Disorder
- bipolar disorder
- Schizoaffective Disorders
- Tourette’s Syndrome
- Senile Dementia of Alzheimer type
*NRL - neuroleptic
**DO - disorder
 - Mesoridazine
- Major metabolite of thioridazine
- More potent than the parent compound
- Haloperidol(Haldol©)
- non-selective neuroleptic
- EPS is common

- Thiothixene
- Same structure as phenothiazine but N replaced by C

Atypical Antipsychotics
- Clozapine
- Antipsychotic effects : 5-HT 2A/2C and D2 receptor
Antipsychotic – excess dopamine (needs blockage) antagonism.
Parkinson – low dopamine - More potent antagonism at the D4 than D2 receptor.
- Lowest likelihood EPS and tardive dyskinesia
- Reserve drug for severely schizophrenic patients who are
refractory to traditional therapy
- Olanzapine (Zyprexa)
- For people who take perphenazine first and get no or
minimal benefit or experience intolerable A/E
- not a good option for overweight, blood sugar
abnormalities, diabetes, or heart disease

Summary of Adverse Effects

➔ ANS
CHEMICAL CLASSIFICATION - Muscarinic receptor blockade:
➔ TYPICAL - Loss of accommodation; Difficulty in urination;
★ Phenothiazines Constipation
★ Aliphatic - Chlorpromazine, Promazine, Trifluoperazine - toxic - confusional state
★ Piperazine - Fluphenazine, Perphenazine, Acetophenazine, ➔ Alpha adrenergic blockade
Trifluorophenarine, Prochlorperazine - Chlorpromazine - Orthostatic hypotension
★ Piperidine - thioridazine - Mesoridazine - Failure to ejaculate;Impotence
★ Butyrophenones - haloperidol ➔ CNS
★ Thioxanthenes - Chlorprothixene and Thiothixene - Dopamine receptor blockade
➔ EPS
➔ATYPICAL ➔ Prolactin elevation
★ Dihydroindolines - molindone - Amenorrhea, galactorrhea, infertility
★ Diphenylbutylpiperidine - pimozide ➔ Dopamine receptor hypersensitivity
★ Dibenzoxazepine - clozapine - Tardive dyskinesia (involuntary movements)
★ Benzisoxazole - Risperidone - Tardive akathisia (extreme restlessness)
★ Thienobenzodiazepine - Olanzapine - Endocrine - Hyperprolactinemia
★ Fluorophenyl Indole - quetiapine - Serotonin 5-HT2 blockade
➔ Potency ★ Piperazine → Piperidine → Aliphatic - Orthostatic hypotension
- Sedation
★ Phenothiazines - Weight gain
- Chlorpromazine
- First antipsychotic developed as a surgical anesthetic MOVEMENT DISORDERS
- Receptors blocked: Extrapyramidal Symptoms (EPS)
- Adrenoceptors-Hypotension - AKA neuroleptic-induced parkinsonism
- Serotonin - Most common (15%)
- Histamine 1 - sedation - Coarse tremors, rigidity, bradykinesia
- Muscarinic - Constipation, dryness - Risk: high potency
- Dopamine blockade - Parkinsonian syndrome - Treatment: lower dose, anticholinergics
*NRL - neuroleptic
**DO - disorder
Acute Dystonia
- Muscular spasm, involuntary movement
- Spasmodic torticollis, trismus, tongue protrusion,
opisthotonos , upward mov’t of eyes (oculogyric crisis)
- Risk: high-potency antipsychotics
- Onset: early in tx (days)
- Treatment: IM/IV anticholinergics (benztropine,
diphenhydramine, biperiden)

Akathisia
- Subjective feeling of muscular discomfort
- Agitated, pace relentlessly, alternately sit and stand
- Risk: recent increase/onset of meds
- Onset: 1 st month of therapy
- Treatment: beta-blockers (propranolol), BZDs (lorazepam),
clonidine

Neuroleptic Malignant Syndrome (NMS)

- idiosyncratic, life-threatening
- Motor: Muscular rigidity, dystonia, agitation
- Autonomic: hyperpyrexia, hypertension
- Risk: high-dose, rapid dose escalation; IM injection, prior
history
- Onset: usually within first few weeks
- Treatment: discontinue meds, supportive, dantrolene,
bromocriptine

Tardive Dyskinesia
- choreoathetoid movements
- Tongue protrusion/twisting,lip puckering
- Risk: elderly, long-term treatment, female
- Onset: years after treatment
- Treatment: lower dose, change meds

OTHER ADVERSE EFFECTS

- Agranulocytosis - clozapine, chlorpromazine
- Pigmentary retinopathy - thioridazine
- ECG changes - prolonged QT interval ziprasidone

OTHER USES OF ANTIPSYCHOTICS

- Antiemetic (blocks dopamine receptors) -
prochlorperazine
- Intractable hiccups - chlorpromazine
- Pruritus (antihistamine) - promethazine (Zinmet,
Thaprozine)

*NRL - neuroleptic
**DO - disorder