Clinical (psychiatric) Disorders

• Disorders diagnosed at childhood (ADHD)
• Dementia and delirium
• Psychotic disorders (schizophrenia)
• Affective disorders (major depression, bipolar disorders)
• Anxiety disorders (OCD, panic disorders, etc)
• Somatoform disorders (hypochondriasis)
• Dissociative disorders (personality disorders, DID)
• Substance use disorders (alcohol, cocaine)
• Eating disorders
• Sleep disorders

Personality Disorders, Mental Retardation

General Medical Conditions

Diabetes, HTN

Psychosocial and Environmental Problems

Homeless, divorce, education problems, unemployed, abusive relationship

Mental Status Exam:

AMSIT

Appearance

Mood and Affect

Sensorium (orientation, memory, calculations)

Intelligence

Thought (form, content, abstract ability)

• involuntary movements (extrapyramidal system)
• hyperprolactinemia
• decrease in positive symptoms

• psychosis
• antiparkinsonian effect
• psychomotor activation
• enhanced motivation and cognition

• Suppresses excess activity (seizures)
• Alcohol, benzodiazepines, barbiturates act here

• Muscle relaxation
• GHB, baclofen act here

• Hallucinations
• Delusions
• Disorganized thinking
• Disorganized behavior

• Flat affect
• Alogia
• Avolition
• Asociality
• Anhedonia
• Ambivalence
• Lack of insight/judgement

DSM-IV-TR

Diagnosis of Schizophrenia

1. Active Psychotic Symptoms > 1 month

• > 2 of the following: delusions, hallucinations, disorganized speech, disorganized behavior, negative symptoms
• Only 1 criteria is necessary if delusions are bizarre or hallucinations are running commentary

2. Social/Occupational Dysfunction: Functioning below the highest expected level

3. Duration of Illness: > 6 months

4. Schizoaffective and Mood Disorder Exclusion

5. Substance/General Medical Condition Exclusion

• Early stages of schizophrenia
• Social isolation or withdrawal
• Impairment of functioning
• Impaired personal hygeine
• Blunted Affect

2 mg BID-TID

Max 20 mg/day

Haloperidol

Fluphenazine

Thiothixene

Trifluoperazine

Acute Psychotic Agitation

Aggression

Positive Symptoms

Dose: 50 mg/ml, 100 mg/ml

Intramuscular Injection

Sesame oil vehicle, slowly absorbed at IM site

Dose conversion: 10-15 x daily PO dose Haldol q month

Adv

• Better for + symptoms of schizophrenia
• Generic (cheaper)

Disadv

• Possible worsening of - symptoms
• Induces EPS

Adv

• More commonly used; 1st line therapy
• + and - symptoms improve, but better for + symptoms of schizophrenia
• May enhance cognitive functioning
• Less risk for EPS

Disadv

• More likely to see metabolic complications (diabetes, weight gain)

EPS --> related to high D2 blockade

Anticholinergic

Molindone

Loxapine

Perphenazine

Weight neutral

Possible weight loss with use

Low Potency FGAs

Chlorpromazine

Thioridazine

• More sedating side effects (H1 blockade)
• Orthostatic hypotension (Alpha1 blockade)
• High incidence of anticholinergic side effects (dry mouth, constipation, urinary retention, blurred vision, memory impairment)

NOT first-line agents

• Haldol for psychosis and agitation
• May also give Thorazine (chlorpromazine) or Prolixin (Fluphenazine)
• Cogentin (benztropine) to avoid EPS (dystonic reaction)
• Ativan for sedation and minimize agitation

EPS: Acute Dystonia

What it is, Treatment

• Sustained and painful muscle contractions involving the neck, back, eyes, larynx (laryngospasm can be fatal)
• Occurs hours to days after initiation of medication
• Risk factors: young, male, high doses of high potency FGAs

Treatment

• IM benztropine (cogentin) 2 mg

OR

• IM diphenhydramine (bendaryl) 25-50 mg

EPS: Akathisia

What it is, Treatment

• Restlessness, pacing, foot tapping, anxiety, agitation
• Occurs days to weeks after initiation of medication
• Often misdiagnosed as agitation or worsening psychosis

Treatment

• Beta blockers (propranolol) 30-120 mg/day

OR

• Benzodiazepines (lorazepam-Ativan)

EPS: Pseudoparkinsonism

What it is, Treatment

• Mask-like face, shuffled gait, stooped posture, drooling, resting tremor, rigidity, cogwheeling, pill-rolling
• Occurs weeks to months after initiation of medication
• Risk factors: elderly, female, high-dose antipsychotics

Treatment

• Benztropine (Cogentin) 1-8 mg/day
• Trihexyphenidyl (Artane) 2-15 mg/day (divided)

EPS: Tardive Dyskinesia

What it is, Treatment

• Smooth abnormal movements in mouth, face, eyes, hands, back or trunk
• Occurs month to years after initiation of medication
• Risk factors: long duration of treatment with typical antipsychotics, older age, female, high dose antipsychotic
• Possibly irreversible
• AIMS (Abnormal Involuntary Movement Scale) q 6 months

Treatment (prevention is best tx)

• Use lowest effective dose
• Switch to atypical agent or clozapine
• Reevaluate need for antipsychotic
• Vitamin E?? --> increases risk for cardiovascular complications

Neuroleptic Malignant Syndrome (NMS)

What it is, Treatment

• Symptoms: Muscle rigidity, hyperthermia, changes in mental status, autonomic dysfunction (changes in BP, tachycardia)
• Labs: Increase CPK

Treatment

• D/c antipsychotic, supportive care, dopamine agonist (bromocriptine), and/or smooth muscle relaxant (dantrolene)
• Emergency medical treatment

• Clozapine
• Risperidone
• Olanzapine
• Quetiapine
• Ziprasidone
• Aripiprazole
• Paliperidone
• Asenapine
• Iloperidone

5HT-2 > D2

• 5HT-2 blockade in mesocortical area may enhance DA transmission (relieving (-) symptoms)
• Less risk of TD and EPS -- however EPS has been reported with most atypicals

• Weight gain
• Hyperglycemia
• New onset of Diabetes Mellitus

Quetiapine > Clozapine > Ziprasidone > Olanzapine > Aripiprazole > Risperidone

• The faster the dissociation, the less likely EPS will develop
• Risperidone binds tightly to D2 receptors, thus it is more likely to cause EPS
• Fast dissociation usually = BID dosing

Release of DA in nigrostriatal pathway and NOT in the mesolimbic pathway (minimal 5-HT_2A receptors)

• Decreases violence and aggression
• Treats refractory psychosis
• Reduces suicidal ideation
• Improves tardive dyskinesias
• Least likely to cause EPS

• Life-Threatening Agranulocytosis
• Seizure-risk (higher doses)
• Sedation (H1 and M1)
• Weight gain (H1 and 5-HT_2C antagonism)
• Hyperlipidemia/Hyperglycemia
• Sialorrhea
• Anticholinergic effects (dry mouth, constipation)
• Tachycardia/Myocarditis
• Orthostasis/Hypotension (alpha1 antagonism)
• Respiratory depression

CBC with differential:

• ANC < 500/mm3

In order to start Clozapine:

• WBC must be > 3500/mm3
• ANC must be > 2000/mm3

• Flu-Like Symptoms
• Fever
• Sore Throat
• Easy Bruising
• Mouth Ulcers

• History of drug-induced dyscrasia
• Uncontrolled seizure disorder
• WBC < 3500 cells/mm3
• History of a myeloproliferative disorder
• Current pregnancy (relative)
• < 16 yo (relative)
• Paralytic ileus

• Brief Psychiatric Rating Scale
• CBC with differential  (within 7 days of initiation)
• Physical examination
• Blood pressure (supine and standing)
• Oral temp
• Pulse (tachycardia not uncommon)
• Pregnancy test
• Recommended tests: ECG, liver function tests (AST, ALT, Alk phos), creatinine, and BUN

CBC with Differential

• Weekly x 6 months
• Biweekly x 6 months
• Monthly (every 28 days)

Eosinophils

• Eosinophilia => 4000/mm3 (hold clozapine)
• Prolonged elevations --> possible hypersensitivity rxn (fever, rash, myalgias, arthralgias) --> release of vasoactive compounds

Initial Dosing:

12.5 mg BID or 25 mg/day

• Increase by 50 mg/day in 1st 2 weeks
• Subsequent increase no more than once or twice weekly and not to exceed 100 mg/day

Max dose = 900 mg/day

NO PRN DOSING

• Phenytoin --> decreases clozapine levels
• Carbamazepine --> agranulocytosis
• Ciprofloxacin --> increase Cloz levels
• Benzodiazepines (lorazepam, clonazepam) --> respiratory depression
• Benztropine or Diphenhydramine --> increased anticholinergic side effects
• Epinephrine (CI) --> hypotension
• Cigarette smoking --> decreased clozapine levels

Dosage: 4-6 mg/day

Maximum: 16 mg/day

Start dosing low and BID for best tolerability

Doses > 6 mg increases risk for EPS

Dosage Forms: tablet, solution, ODT (M-tab), long-acting injection

• Orthostasis (dizziness)
• Weight gain
• EPS
• Increase Prolactin (decreased libido, amenorrhea -- osteoporosis, galactorrhea, gynecomastia)

IM injection given every 2 weeks

Recommended starting dose:

2-4 mg PO --> 25 mg q 2weeks

4-6 mg PO --> 37.5 mg q 2 weeks

6-8 mg PO --> 50 mg q 2 weeks

Water based injection, less painful

Continue PO x 3 weeks

Dosage:

10-20 mg/day

Smokers may require 30-40 mg/day

Max 30 mg/day

Dosage Forms:

tablets, ODT, short acting injection (IM), long acting injection (Relprevv) --> IM admin. with benzodiazepines = severe hypotension

• Sedation
• Dry mouth
• Constipation
• Weight gain
• Hyperlipidemia
• Hyperglycemia/Diabetes

Long-Acting Olanzapine IM Injection

10 mg PO = 210 mg q 2 weeks or 405 q 4 weeks (1st 8 weeks)

Maintenance = 150 mg q 2 weeks or 300 mg q 4 weeks

20 mg PO = 300 mg 2 weeks

Dosage:

300-800 mg/day

Max 800 mg/day

Dosage Forms:

Tablets, ER

• Orthostasis
• Headache
• Sedation
• Weight gain
• Hypertriglyceridemia

Dosage:

80-160 mg/day (given BID)

Bioavailability increases 2x when given with food

Max: 160 mg/day

Dosage Forms:

Capsules, short-acting injection (IM)

Geodon (IM) -- max 2 x 20 mg doses in 24 hr

IM administration with benzodiazepines = severe hypotension

• Insomnia
• Nausea
• Headache
• QTc prolongation longest among atypicals -- ECG required before initiation at some facilities

D2 partial agonist/antagonist

5-HT1A partial agonist

5-HT2A antagonist

Dosage:

10-30 mg/day

Max 30 mg/day

Dosage Form:

tablets, solution, ODT, short-acting IM -- CAN administer benzodiazepines concomitantly with IM

• Insomnia
• Anxiety
• Akathisia
• Headache
• Nausea

Dosage:

6 mg/day (titrate weekly)

Max 12 mg/day

Taken with food increases bioavailability by 60%

Dosage Forms:

OROS capsules, long-acting injection - paliperidone pamitate

• Tachycardia
• Nausea
• Weight gain
• Dizziness
• Anxiety EPS

IM paliperidone

Dosage:

Q monthly

Initial dose -- 234 mg IM deltoid

1 week later: 156 mg IM deltoid

Maintenance dose: IM deltoid or gluteal

39 mg IM = 3 mg PO

117 mg IM = 6 mg PO

234 mg IM = 12 mg PO

Dosage:

5 mg BID

Dosage Form:

sublingual tablet

• Oral hypoesthesia

1 mg BID

Increase to target 12-24 mg/day

• Orthostasis (alpha blocker)
• Dizziness
• Sedation
• HA
• Weight gain
• Nausea