schizophrenia

1

SchizophreniaSchizophrenia

Diagnosis and PharmacotherapyDiagnosis and PharmacotherapyJason Cavolina

Clerkship

Internal Medicine I

2

EpidemiologyEpidemiology

• Incidence: uncommon (~1%)• Prevalence: equal across cultures and sexes• Onset: usually during adolescence and early

adulthood (Male~18-20) (Female~26-30)• Heredity: higher prevalence in 1st degree

biologic relatives w/ schizophrenia• parents w/ schizophrenia have offspring w/ ~40% chance of

schizophrenia

Addapted from DSM IV, Washington, DC; American Psychiatric Association, 1994

3

DiagnosisDiagnosis

• Characteristic psychotic symptoms: exhibited for at least 1 month during the active phase of illness

– Lack of insight – Auditory hallucinations – Ideas of reference – Suspiciousness – Voices speaking to patient– Delusions – Thoughts spoken aloud


4

DiagnosisDiagnosis

• Functioning below previous level: – Work– Interpersonal relations – Self-care

• Signs and symptoms last for at least 6 months: may include prodromal or residual symptoms


5

DiagnosisDiagnosis

• Must rule out:– Schizoaffective disorder– Mood disorder– Medical disorder (organic causes)– Substance abuse

6

Core Symptom Clusters: Core Symptom Clusters:

• Positive Symptoms:– Delusions

– Hallucinations

– Disorganized speech

– Catatonia

• Do respond well to drug therapy (typical and atypical drugs); response to meds seen in ~7-14 days

• Negative Symptoms:– Affective flattening

– Alogia

– Avolition

– Anhedonia

• Do not respond well to typical drugs (do respond to atypical drugs); response to meds seen in ~6 months

7

Core Symptom Clusters:Core Symptom Clusters:

• Cognitive symptoms: – Attention– Memory– Executive functions

• Mood symptoms:– Dysphoria– Suicidality– Hopelessness

Social / Occupational Dysfunctions

8

Favorable Prognostic Factors: Favorable Prognostic Factors: • Female sex • Good social support network• High IQ• Abrupt onset of illness• Presence of positive

symptoms • Presence of stressful

precipitating events

• Associated mood disturbances• Good insight• Fast tx after 1st episode• Good medication adherence• Good interepisode functioning• Absence of brain abnormalities• Family history + mood disorder

and – schizophrenia

9

PharmacotherapyPharmacotherapy

• Typical antipsychotics • 1st generation• Low Potency:

– Chlorpromazine [THORAZINE]: dose range 300-1000 mg/d

– Thioridazine [MELLARIL]: dose range 100-800 mg/d; high doses lead to pigmentary retinopathy (need eye exams), and QT interval

– Mesoridazine [SERENTIL]: metabolite of thioridazine

10


• Typical antipsychotics • 1st generation• High Potency:

– Fluphenazine [PROLIXIN]: dose range 5-20 mg/d• Fluphenazin D: deconate; long-acting IM form for

maintenance therapy in non-compliant patients; dose range 6.25-50 mg IM/ 2-4 weeks

– Haloperidol [HALDOL]: dose range 2-20 mg/d• Haloperidol D: dose range 50-200 mg/2-4 weeks

– Thiothixene [NAVANE]: dose range 15-50 mg/d– Trifluoperazine [STELAZINE]: dose range 5-40 mg/d

11


• Typical antipsychotics • 1st generation• High Potency:

– Loxapine [LOXITANE]: dose range 50-150 mg/d

– Molindone [MOBAN]: dose range 50-150 mg/d– Perphenazine [TRILAFON]: dose range 16-64 mg/d

12


• Atypical Antipsychotics• 2nd generation• 1st line therapy

– Effective against: negative and positive symptoms

– Treatment resistant patients

– Less prolactin effect

– Lower risk of EPS / TD– Do not cognitive function

13


• Atypical Antipsychotics:– Clozapine [CLOZARIL]: dose range 300-900 mg/d

(given BID 1/3 AM 2/3 PM); serum levels at doses >600 mg/d

• Side Effects: agranulocytosis, seizures, myocarditis, anticholinergic effects, salivation, weight gain

• Usually reserved for tx resistant patients b/c of side effect profile

– Olanzapine [ZYPREXA]: dose range 10-20 mg/d• Side Effects: weight gain and sedation (dosing given HS)

– Quetiapine [SEROQUEL]: dose range 300-800 mg/d (given BID)

• Side Effect: weight gain (monitor TG, cholesterol, LFT)

14


• Atypical Antipsychotics cont:– Risperidone [RISPERDAL]: dose range 2-6 mg/d (given HS or

AM); > 6 mg/d lead to EPS– Ziprasidone [GEODON]: dose range 80-160 mg/d (divided BID)

[food can absorption two-fold]• NO weight gain, orthostasis, or sedation are seen

– Aripiprazole [ABILIFY]: dose range 10-30 mg/d (given QD)• Partial DA agonist: antagonist during high DAergic activity

(mesolimbic DA, psychotic symptoms); agonist during low DAergic activity (low EPS or negative symptoms)

• Partial serotonin agonist• No prolactin or anticholinergic effects • Minimal weight gain, hypotension and sedation

15


• Injectable Agents: – Acute Agitation: haloperidol, olanzapine,

ziprasidone; (can use a lower dose if combined with a benzodiazepine)

– Maintenance therapy: used for patients who exhibit poor compliance; risperdal consta (given q2w); haldol deconate (q4w); or prolixin deconate (q2-3w)

• For patients who “cheek” their meds give risperdal M-tab (oral disintegrating tablet, ODT)

16

MonitoringMonitoring• Extrapyramidal Side effects: seen mostly in 1st generation

(especially high potency) and w/ risperidone– Acute dystonia: can be life threatening

• Includes: oculogyric crisis; torticollis; opisthotonus; trismus; and spasming of other muscles

• Occurrence: seen usually in young males; 90% occurs w/in 72 hours of tx• Tx: parenteral anticholinergic agents (benztropine [Cogentin]; and/or dose

– Pseudoparkinsonism: • Includes: akinesia (rigidity, immobility, masklike expression, stooped

posture, slow speech); and tremors (especially hands)• Occurrence: seen usually in elderly females; occurs ~3 months into therapy

– Akathisia: least responsive to drug therapy• Includes: inability to sit still; restless movement; and tapping of feet• Tx: prevent with inderal; and/or dose; and/or give BZD’s

17

MonitoringMonitoring

• Tardive dyskinesia: 1st generation drugs– Includes:

• Choreiform movements

• Athetoid movements

• Axial hyperkinesis

– Abnormal Involuntary Movement Scale: (AIMS) measures progression of TD; performed every 6 months

– Tx: mild to moderate change to 2nd gen drug; severe change to clozapine

18


• Neuroleptic Malignant Syndrome (NMS): potentially fatal and can occur at any time; seen more with 1st generation drugs

– Includes: high fever; WBC; muscular rigidity; CPK– Tx: fluids; ICU; respiratory support; d/c drug

• Sedation: seen mostly w/ low potency typical meds• Hyperprolactinemia: seen with typical meds and

risperdidone– Signs and Symptoms: galactorrhea, gynecomastia, sexual

dysfunction, and amenhorrhea

19


• Anticholinergic effects: seen mostly w/ low potency 1st generation drugs

• Orthostatic Hypotension: seen mostly w/ low potency 1st generation drugs

• QTc interval prolongation: > 0.44s seen with thioridazine

20


• Weight gain: most common with atypicals clozapine and olanzapine (not as common, but still seen, with risperidone, quetiapine and typical drugs)

• Ophthalmic effects: thioridazine causes pigmentary retinopathy (atrophy and pigment infiltration)

• Seizures: mostly seen with low potency typical drugs and clozapine; minimize with slow dose titration and use of lowest effective dose

21


• Sexual Dysfunctions: most common with thioridazine but can be seen with any typical or atypical agents

• Agranulocytosis: seen with clozapine ~ 1-2% – Risk: seen @ 6-18 weeks; in female, elderly, and cachectic

patients– Do not start if: WBC <3.5 K/mm3

– D/C permanently if: WBC <2.0 K/mm3

– D/C temporarily if: WBC <3.0 K/mm3

• Warning signs: pharyngeal infections; fever• Monitoring: baseline, weekly, then every 4 weeks after D/C drug

22


• Drug Interactions: – Dopamine receptor antagonists +

• Anticonvulsants: dopamine antagonists anticonvulsant levels• Antihypertensives: dopamine antagonists potentiate hypotension• Barbiturates: long term use will antipsychotic levels; short term

use will CNS depressant effects• Levodopa; mutual antagonism between levodopa and dopamine

receptor antagonist• Pressor agents:

– α-agonists: pressor effect is antagonized– β-agonists: marked hypotension

• Sedative-Hypnotics: additive CNS depressant effects

23

MonitoringMonitoring• CYP450 Drug Interactions: • Clozapine: major 1A2; minor 3A4

and 2D6– Inhibited by: cimtidine;

erythromycin; fluoxetine; paroxetine; fluvoxamine; and quinidine

– Induced by: smoking; carbemazepine; and phenytoin

• Olanzapine: major 1A2; minor 3A4 and 2D6

– Inhibited by: fluvoxamine– Induced by: smoking

• Quetiapine: major 3A4; minor 2D6– Inhibited by: cimetidine,

erythromycin; fluconzaole; itraconazole; and ketoconazole

– Induced by: carbamezapine and phenytoin

• Risperidone: major 2D6– Inhibited by: fluoxetine; paroxetine;

and quinidine• Ziprasidone: major aldehyde oxidase;

minor 3A4 and 1A2– Induced by: carbemazepine

• Aripiprazole: major 3A4; minor 2D6 (see quetiapine above)

• Thioridazine: avoid all drugs that inhibit 2D6 ( QTc interval)

24


• Efficacy:• Acute Phase:

hostility and aggression; relieve acute symptoms to functioning

• Stabilization Phase: ~ 6+ months after onset of acute symptoms

stress, symptoms (see +/-)• Stable Phase: symptoms stable or not present or

less severe– Pt may exhibit anxiety, tension, depression, and

insomnia (add adjunctive tx)

25

ReferencesReferences• Lexi-interact Lexi-comp hand held reference, 2005 • Lexi-onhand. Lexi-complete and specialties. Updated 8/05• http://www.clevelandclinicmeded.com/diseasemanagem

ent/psychiatry/schizophrenia/table1schizo.htm , accessed 9/20/05

• http://www.clevelandclinicmeded.com/diseasemanagement/psychiatry/schizophrenia/schizophrenia.htm#table1 , accessed 9/20/05

• http://depts.washington.edu/stellalb/images/Schizophrenia.pdf , accessed 9/20/05

• http://www.mentalhealth.com, accessed 9/20/05• http://www.psych.org/research/dor/dsm/index.cfm ,accessed

9/20/05• Micromedex Drugdex system 2005, accessed, 9/19/05

schizophrenia

Documents