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http://emedicine.medscape.com/article/294763-overview

Schizoaffective Disorder

Author: Guy E Brannon, MD, Associate Clinical Professor of Psychiatry, Louisiana StateUniversity Health Sciences Center; Director, Adult Psychiatry Unit, Chemical Dependency Unit,

Clinical Research, Brentwood Behavior Health CompanyContributor Information and Disclosures

Updated: Jun 3, 2009

Introduction

Background

The term schizoaffective disorder was coined by Dr. Jacob Kasanin in 1933. Schizoaffectivedisorder is a perplexing mental illness distinguished by a combination of symptoms of a thought

disorder or other psychotic symptoms such as hallucinations or delusions (schizophreniacomponent) and those of a mood disorder (depressive or manic component). The coupling of

symptoms from these divergent spectrums makes treating patients who are schizoaffectivedifficult.

Schizoaffective disorder is defined using theDiagnostic and Statistical Manual of Mental

Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria or byInternational Classificationof Diseases, Tenth Revision (ICD-10) coding. Schizoaffective disorder has features of both

schizophrenia, including hallucinations, delusions, and distorted thinking, and a moodcomponent, such as depression or mania.

The diagnosis is made when the patient has features of both illnesses but does not strictly meet

diagnostic criteria for either schizophrenia or a mood disorder alone. Unfortunately, determiningif a patient has 2 separate illnesses (schizophrenia or a mood disorder), a combination of illnesses

(schizophrenia and a mood disorder), or perhaps even a distinct and separate illness apart fromschizophrenia or a mood disorder is difficult. Making the diagnosis of schizoaffective disorder

can be difficult because it encompasses 2 other diagnostic entities, namely schizophrenia andmood disorders. An accurate diagnosis is made when the patient meets criteria for major

depressive disorder or mania while also meeting the criteria for schizophrenia. Moreover, thepatient must have psychosis for at least 2 weeks without a mood disorder.

Men with schizoaffective disorder tend to exhibit antisocial personality traits. The age of onset islater for women than for men, and the exact etiology and epidemiology is unclear because of

limited research in this area. Patients with schizoaffective disorder are thought to have a betterprognosis than that of patients with schizophrenia. Treatment consists of both pharmacotherapy

and psychotherapy.

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Sex

Schizoaffective disorder is more common in women than in men. Men with schizoaffective

disorder tend to exhibit antisocial traits and behavior in contrast to other personality traits. Inaddition, the age of onset is later for women than for men, and the exact etiology and

epidemiology is unclear because of limited research in this area.

Age

Young people with schizoaffective disorder tend to have a diagnosis with the bipolar subtype,

whereas older people tend to have the depressive subtype.

Clinical

History

y Diagnostic criteria for schizoaffective disorder are as follows:4o An uninterrupted period of illness occurs during which a major depressive episode, a

manic episode, or a mixed episode occurs with symptoms that meet criterion A for

schizophrenia. The major depressive episode must include criterion A1, ie, depressed

mood.

o During the same period of illness, delusions or hallucinations occur for at least 2 weeks,in the absence of prominent mood symptoms.

o Symptoms that meet the criteria for mood episodes are present for a substantial portionof the total active and residual periods of illness.

o The disturbance is not due to the direct physiologic effects of a substance (eg, illicitdrugs, medications) or a general medical condition.

o The bipolar type is diagnosed if the disturbance includes a manic or a mixed episode (ora manic or a mixed episode and major depressive episodes).o The depressive type is diagnosed if the disturbance includes only major depressive

episodes.

Physical

Obtain a complete medical history, and perform a complete mental status examination, physical

examination, and neurologic examination to assist with the evaluation and rule out other disease

processes.

Although the mental status examination varies for each patient, examples of items to assess arelisted below. Because of the variability of the presentation of the disorder, any or all symptomsof schizophrenia, bipolar disorder, or major depressive disorder may manifest depending on the

presenting subtype.

y Appearance - Ranges from well-groomed to disheveledy Eye contact - Appropriate, increased, or decreasedy Facial expression - Neutral, angry, euphoric, sad

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y Motor - Possible psychomotor agitation or retardationy Cooperativeness -May cooperate or may be uncooperativey Mood - Euthymic, depressed, or manicy Affect - Ranges from appropriate to flaty Speech - Ranges from poverty to flight of ideas or pressuredy Suicidal ideation - May or may not be present. Remember that individuals with this disorder

have a lifetime risk for suicide, which is significant. Inquiring about suicidal ideation at each visit

is always important. In addition, the interviewer should inquire about past acts of self-harm or

violence. Ask the following types of questions when determining suicidal ideation or intent. "Do

you have any thoughts of wanting to harm or kill yourself?" "Do you have any thoughts that you

would be better off dead?" If the reply is positive for these thoughts, inquire about specific

plans, suicide notes, family history (anniversary reaction), and impulse control. Also, ask how the

patient views suicide to determine if a suicidal gesture or act is ego-syntonic or ego-

dystonic. Next, determine if the patient will contract for safety.

y Homicidal ideation - May or may not be present. Inquiring about homicidal ideation or intentduring each patient interview is also important. Ask the following types of questions to help

determine homicidal ideation or intent. "Do you have any thoughts of wanting to hurt

anyone?" "Do you have any feelings or thoughts that you wish someone were dead?" If thereply to one of these questions is positive, ask the patient if he or she has any specific plans to

injure someone and how he or she plans to control these feelings if they occur again.

y Orientation - To elicit responses concerning orientation (ie, person, place, time, situation), askthe patient questions, as follows. "What is your full name?" "Do you know where you are?"

"What is the month, date, year, day of the week, and time?" "Do you know why you are here?"

y Consciousness - Levels of consciousness are determined by the interviewer and are rated as (1)coma, characterized by unresponsiveness; (2) stuporous, characterized by response to pain; (3)

lethargic, characterized by drowsiness; and (4) alert, characterized by full awareness.

y Concentration and attention - Ask the patient to subtract 7 from 100, then to repeat the taskfrom that response. This is known as serial 7s. Next, ask the patient to spell the word world

forward and backward.y Reading and writing - Ask the patient to write a simple sentence (noun/verb). Then, ask patient

to read a sentence (eg, "Close your eyes."). The part of the MMSE evaluates the patient's ability

to sequence.

y Memory - To evaluate a patient's memory, have him or her respond to the following prompts.For remote memory, "What was the name of your first grade teacher?" For recent memory,

"What did you eat for dinner last night?" For immediate memory, "Repeat these 3 words: pen,

chair, flag." Tell the patient to remember these words.Then, after 5 minutes, have the patient

repeat the words.

y Delusions - Any type possible (eg, paranoid, thought insertion or withdrawal, grandiose, bizarre,to name a few)

y Hallucinations - Any type possible (most common is auditory, least common is gustatory)y Insight - Range variesy Judgment - Range varies

Causes

Although the cause of schizoaffective disorder is unknown, the cause may be similar to

schizophrenia nature versus nurture. To date, no specific genetic markers have been identified.Environmental causes of malnutrition, viral infections, or complication at birth may play a role.

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Finally, abnormalities of the neurotransmitters serotonin, norepinephrine, and/or dopamine couldall have a role in this disorder. More research is needed to fully elucidate the causes of

schizoaffective disorder.

Differential Diagnoses

Amphetamine-Related PsychiatricDisordersHIVDisease

Bipolar Affective Disorder Hyperparathyroidism

Brief Psychotic Disorder Phencyclidine (PCP)-Related PsychiatricDisorders

Cocaine-Related PsychiatricDisorders Schizophrenia

Cushing Syndrome

Depression

Hallucinogens

Other Problems to Be Considered

Steroid use

Temporal lobe epilepsyComplex partial seizure disorder

NeurosyphilisThyroid problems

Alcohol abuse or dependenceMetabolic syndrome

Delirium

Narcolepsy

Workup

Laboratory Studies

y Sequential multiple analysisy Complete blood cell county Rapid plasma reagenty Test of thyroid-stimulating hormone or thyroid function testsy Urine drug screeny Urine pregnancy testy Urinalysisy Lipid panely HIV test

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Imaging Studies

y If the patient's neurologic findings are abnormal, CT or MRI rule out any suspected intracranialpathology may be appropriate.

Other Tests

y Perform psychological testing to assist with diagnosis (eg,Structured Clinical Interview for Axis IDSM-IVDisorders [SCID-1]).

y Several scales are available for rating the severity of disease in patients with schizophrenia orschizoaffective disorder.

o These scales may be useful in assessing the patient's progress (eg, Positive and NegativeSymptom Scale for Schizophrenia [PANSS]).

o These scales include those for positive and negative symptoms and many for depressionand bipolar rating (eg,Hamilton depression scale, Young mania scale). These tools can

be used for baseline and outcome measurements.

o The cut down, annoyed, guilty, and eye opener (CAGE) Questionnaire is useful to inquireabout alcohol consumption in patients with schizoaffective disorder.

y Perform electroencephalography, if indicated.Histologic Findings

Findings include decreased amounts of cortical gray matter and increased fluid-filled spaces.

Treatment

Medical Care

y If patients are suicidal, homicidal, or gravely disabled, admit them to an inpatient psychiatricunit. Inpatient treatment is mandatory for patients who are dangerous to themselves or othersand for patients who cannot take care of themselves.

y Patients who have schizoaffective disorder can greatly benefit from psychotherapy and well aspsychoeducational programs.

o They should receive therapy that involves their families, develops their social skills, andfocuses on cognitive rehabilitation.

o Psychotherapies should include supportive therapy and assertive community therapy inaddition to individual and group forms of therapy and rehabilitation programs.

y Family involvement is needed in the treatment of this particular disorder.y Treatment includes education about the disorder and its treatment, family assistance in

compliance with medications and appointments, and maintenance of structured daily activities

(ie, schedule of daily events) for the patient.

Consultations

y Consult a neurologist to rule out neurological disease.

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Diet

y No specific diet is recommended for patients with schizoaffective disorder.Activity

y Restrict activity if patients represent a danger to themselves or to others or if they are gravelydisabled. Otherwise, encourage patients who are schizoaffective to continue their normal

routines and strengthen their social skills whenever possible.

Medication

Several medications are used to treat schizoaffective disorder. Agent selection depends on

whether the depressive or manic subtype is present. Early treatment with medication along withgood premorbid function often improves outcomes. In the depressive subtype, combinations of

antidepressants (eg, sertraline, fluoxetine) plus an antipsychotic (eg, haloperidol, risperidone,olanzapine) are used. In refractory cases, clozapine has been used as an antipsychotic agent. In

the manic subtype, combinations of mood stabilizers (eg, lithium, carbamazepine, divalproex)plus an antipsychotic are used. Of the many medications and combinations available to treat

schizoaffective disorder, a few are reviewed below.

Antipsychotics

These agents ameliorate psychosis and aggressive behavior.

Haloperidol (Haldol)

For management of psychosis. Also for motor and vocal tics in children and adults. Mechanism

of action not clearly established, but has selective effect on CNS by competitively blockingpostsynaptic dopamine (D2) receptors in mesolimbic dopaminergic system; increases in

dopamine turnover responsible for tranquilizing effect. With subchronic therapy, depolarizationblockade and D2 postsynaptic blockade responsible for antipsychotic action.

y Dosingy Interactionsy Contraindicationsy Precautions

Adult

0.5-5 mg PO bid; 2-5 mg IM q4-8h

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Pediatric

12 years: Administer as in adults

y Dosingy Interactionsy Contraindicationsy Precautions

May increase serum concentration of tricyclic antidepressants and hypotensive action of

antihypertensive agents; phenobarbital or carbamazepine may decrease effects; coadministrationwith anticholinergics may increase intraocular pressure; encephalopathic syndromes associatedwith concurrent lithium

y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity; narrow-angle glaucoma; bone marrow suppression; severe cardiac

or liver disease; severe hypotension; subcortical brain damage

y Dosingy Interactionsy Contraindicationsy Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; mayuse if benefits outweigh risk to fetus

Precautions

Severe neurotoxicity (eg, rigidity, inability to walk or talk) may occur in patients with

thyrotoxicosis also receiving antipsychotics if IV/IM, watch for hypotension; caution indiagnosed CNS depression or cardiac disease; in history of seizures, benefits must outweigh risk;

significant increase in body temperature may indicate intolerance to antipsychotics (discontinueif occurs); elevates prolactin levels

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Risperidone (Risperdal)

Selective monoaminergic antagonist binds to dopamine D2 receptor with 20 times lower affinity

than to 5-HT2 receptors. Also binds to alpha1-adrenergic receptors with lower affinity to H1-histaminergic and alpha2-adrenergic receptors. Improves negative symptoms of psychosis and

decreases occurrence of extrapyramidal effects.Also available in long-acting IM formulation (Risperdal Consta).

y Dosingy Interactionsy Contraindicationsy Precautions

Adult

0.25-6 mg/d PO qd/bid

Pediatric

Not established

y Dosingy Interactionsy Contraindicationsy Precautions

Coadministration with carbamazepine may decrease effects; may inhibit effects of levodopa;clozapine may increase levels

y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity

y Dosingy Interactionsy Contraindicationsy Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may

use if benefits outweigh risk to fetus

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Precautions

Extrapyramidal reactions, tachycardia, arrhythmias, orthostatic hypotension, seizures, dysphasia,

hyperprolactinemia, cognitive and motor impairment, priapism, and rare thromboticthrombocytopenia purpura

Olanzapine (Zyprexa)

Atypical antipsychotic with broad pharmacologic profile across receptor systems (eg, serotonin,

dopamine, cholinergic muscarinic, alpha adrenergic, histamine). Antipsychotic effect from

antagonism of dopamine and serotonin type 2 receptors. Indicated for treatment of psychosis andbipolar disorder.

y Dosingy Interactionsy Contraindicationsy Precautions

Adult

5-10 mg/d PO, increase to 10-15 mg/d within 5-7 d; adjust by 5 mg/d q1wk; doses >15 mg/d not

evaluated

Pediatric

Not established

y Dosingy Interactionsy Contraindicationsy Precautions

Fluvoxamine may increase effects; antihypertensives may increase risk of hypotension and

orthostatic hypotension; levodopa, pergolide, bromocriptine, charcoal, carbamazepine,omeprazole, rifampin, and cigarette smoking may decrease effects

y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity

y Dosingy Interactions

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y Contraindicationsy Precautions

Pregnancy

C -F

etal risk revealed in studies in animals but not established or not studied in humans; mayuse if benefits outweigh risk to fetus

Precautions

Caution in narrow-angle glaucoma, cardiovascular disease, cerebrovascular disease, prostatic

hypertrophy, seizure disorders, hypovolemia, paralytic ileus, heat exposure, and dehydration

Clozapine (Clozaril)

Weak D2-receptor and D1-receptor blocking activity, but noradrenolytic, anticholinergic,antihistaminic, and arousal reaction inhibiting effects are significant. Antiserotonergic properties.

Risk of agranulocytosis limits use to patients nonresponsive to or intolerant of classic neurolepticagents.

y Dosingy Interactionsy Contraindicationsy Precautions

Adult

12.5 mg PO qd/bid, increase 25-50 mg/d as tolerated to a therapeutic target of 300-450 mg/d

after 2 wk; titrate to avoid hypotension, seizure, and sedation

Pediatric

Not established

y Dosingy Interactionsy Contraindicationsy

Precautions

Enhances CNS effects of alcohol, MAOIs, and CNS depressants (ie, narcotics, antihistamines,benzodiazepines); increased risk of circulatory collapse leading to cardiac and/or respiratory

arrest with benzodiazepine or other antipsychotic agent; risk of additive effects withanticholinergic, hypotensive, or respiratory depressants; increased plasma levels and toxicity

with warfarin; enhanced metabolism and/or decreased plasma levels with phenytoin,carbamazepine, rifampicin, and St John's wort; increased toxicity and serum levels with

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fluoxetine, paroxetine, sertraline, and fluvoxamine; increased risk of neuroleptic malignantsyndrome occurring with lithium; decreases effectiveness of epinephrine

y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity; WBC count

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Pediatric

Not established

y Dosingy Interactionsy Contraindicationsy Precautions

May antagonize levodopa and dopamine agonists; phenytoin, thioridazine, and other liver

enzyme inducers may reduce levels; CYP450 3A inhibitors (eg, ketoconazole, fluconazole,erythromycin) increase serum concentration

y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity

y Dosingy Interactionsy Contraindicationsy Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may

use if benefits outweigh risk to fetus

Precautions

May induce orthostatic hypotension associated with dizziness, tachycardia, and syncope;

neuroleptic malignant syndrome and tardive dyskinesia have been associated with this treatment

Ziprasidone (Geodon)

Antagonizes dopamine D2, D3, 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1D, alpha1-adrenergic. Hasmoderate antagonistic effect for histamine H1. Moderately inhibits reuptake of serotonin andnorepinephrine.

y Dosingy Interactionsy Contraindicationsy Precautions

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Adult

20 mg PO bid initially; may increase q2-3d to 80 mg PO bid; not to exceed 160 mg/d

Alternative: 10-20 mg IM for rapid tranquilization, as required, to maximum 40 mg/d; 10 mgmay be administered q2h; 20 mg may be administered q4h to maximum 40 mg/d; IM

administration for > 3 d not studied; if long-term therapy indicated, replace IM with PO as soonas possible

Pediatric

Not established

y Dosingy Interactionsy Contraindicationsy Precautions

CYP450-3A4 inhibitors (eg, erythromycin, ketoconazole) may increase serum levels; CYP450-3A4 inducers (eg, carbamazepine, rifampin) may decrease serum levels; coadministration with

drugs that increase QT/QTc interval (eg, amiodarone, fluoroquinolones) increases risk of life-threatening arrhythmias; amphetamines may decrease efficacy of ziprasidone; ziprasidone may

decrease efficacy of levodopa

y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity; history of prolonged QT

y Dosingy Interactionsy Contraindicationsy Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; mayuse if benefits outweigh risk to fetus

Precautions

Prolongs QT/QTc (caution in patients with known risk factors eg, hypomagnesemia,

hypokalemia); caution in seizure disorders; may cause hypotension, extrapyramidal symptoms,and somnolence; hyperglycemia may occur and in some cases be extreme, resulting in

ketoacidosis, hyperosmolar coma, or death

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Aripiprazole (Abilify)

Improves positive and negative schizophrenic symptoms. Mechanism of action unknown, but

hypothesized to differ from that of other antipsychotics. Aripiprazole thought to be partial

dopamine (D2) and serotonin (5HT1A) agonist, and antagonizes serotonin (5HT2A). No QTc-interval prolongation noted in clinical trials.

y Dosingy Interactionsy Contraindicationsy Precautions

Adult

10-15 mg PO qd; if needed, may increase dose gradually q2wk, not to exceed 30 mg/d

Pediatric

Not established

y Dosingy Interactionsy Contraindicationsy Precautions

CYP450 3A4 and 2D6 isoenzyme substrate; therefore, inhibitors (ie, ketoconazole, quinidine,

fluoxetine, paroxetine) or inducers (ie, carbamazepine) may increase or decrease serum levels,respectively

y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity

y Dosingy

Interactionsy Contraindicationsy Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may

use if benefits outweigh risk to fetus

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Precautions

Common adverse effects include headache, anxiety, somnolence, or insomnia; rare reports of

tardive dyskinesia and neuroleptic malignant syndrome; may cause orthostatic hypotension,seizure, dysphagia, or suicidal ideation; hyperglycemia may occur and in some cases be extreme,

resulting in ketoacidosis, hyperosmolar coma, or death

Iloperidone (Fanapt)

Atypical antipsychotic agent indicated for acute treatment of schizophrenia. Precise mechanism

of action unknown. Antagonizes receptors for dopamine-2 and serotonin type 2 (5-HT2).

y Dosingy Interactionsy Contraindicationsy Precautions

Adult

1 mg PO bid initially on day 1; to reach target dose of 12-24 mg/d, adjust dose daily by smallest

possible increments (ie, 2 mg bid on day 2; 4 mg bid on day 3; 6 mg bid on day 4) to avoid

orthostatic hypotension

Pediatric

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y Dosingy Interactionsy Contraindicationsy Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may

use if benefits outweigh risk to fetus

Precautions

Boxed warning: Increased risk of TIAs, CVA, and death with off-label use to treat dementia-

related psychosis in elderly individuals

Common dose-related adverse effects include dizziness, xerostomia, fatigue, nasal congestion,orthostatic hypotension and syncope, tachycardia, and weight gain; serious adverse effects

include QT interval prolongation, neuroleptic malignant syndrome, tardive dyskinesia,hyperglycemia, seizures, leukopenia, neutropenia, agranulocytosis, hyperprolactinemia,

disruption of body temperature, and dysphagia; avoid with hepatic impairment

Antidepressants

These agents decrease aggression and treat the underlying illness.

Selective serotonin reuptake inhibitors (SSRIs) are greatly preferred over the other classes of

antidepressants. Because the adverse-effect profile of SSRIs is less prominent than the profiles ofother drugs, improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk

associated with tricyclic antidepressants. Arrhythmia risk is especially pertinent in overdose, and

suicide risk must always be considered when one treats a child or adolescent with a mooddisorder.

Physicians are advised to be aware of the following information and to use appropriate cautionwhen they consider treatment with SSRIs in the pediatric population.

In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA)issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for

treatment of depressive illness. After review, this agency decided that the risks to pediatricpatients outweigh the benefits of treatment with SSRIs, except fluoxetine (Prozac), which

appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients

younger than 18 years.

In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory

regarding reports of suicidality in pediatric patients being treated with antidepressantmedications for major depressive disorder. This advisory reported suicidality (both ideation and

attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA hasasked that additional studies be performed because suicidality occurred in both treated and

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untreated patients with major depression and thus could not be definitively linked to drugtreatment.

Fluoxetine (Prozac)

SSRI to treat impulse-control problems or underlying illness. Selectively inhibits presynaptic

serotonin reuptake with minimal or no effect in reuptake of norepinephrine or dopamine.

y Dosingy Interactionsy Contraindicationsy Precautions

Adult

10-80 mg PO qd

Pediatric

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Precautions

Caution in hepatic impairment and history of seizures; discontinue MAOIs at least 14 d before

initiating therapy

M

oodS

tabilizer

These drugs stabilize mood associated with bipolar disorder.

Valproic acid, divalproex sodium (Depakote)

May increase brain GABA levels by inhibiting aminobutyrate aminotransferase. GABA inhibitspresynaptic and postsynaptic discharges. In addition to use as mood stabilizer, also used for

migraine headaches, epilepsy, and mania.

y Dosingy Interactionsy Contraindicationsy Precautions

Adult

750 mg/d PO in divided doses; target plasma levels are 50-125 mcg/mL; not to exceed 60mg/kg/d

Pediatric

Initial dose: 10-15 mg/kg/d PO, not to exceed 60 mg/kg/d; if total exceeds 250 mg, should be

given in divided dosages2 years: Benefits outweigh risk but risk of hepatotoxicity decreases considerably

y Dosingy Interactionsy Contraindicationsy Precautions

Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increasetoxicity; rifampin may significantly reduce levels; in pediatric patients, protein binding and

metabolism decrease with concomitant salicylates; coadministration with carbamazepinevariably change carbamazepine concentrations with possible loss of seizure control; may

increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital andphenytoin levels, while either one may decrease valproate levels; may displace warfarin from

protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV-positivepatients

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y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity; hepatic disease; significant disfunction

y Dosingy Interactionsy Contraindicationsy Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Thrombocytopenia and abnormal coagulation parameters have occurred; risk of

thrombocytopenia increases significantly at total trough valproate plasma concentrations >110mcg/mL in females and 135 mcg/mL in males; periodically and before surgery, determine

platelet counts and bleeding time before start of therapy; reduce dose or discontinue therapy ifhemorrhage, bruising, or a hemostasis and/or coagulation disorder occurs; hyperammonemia

may occur, resulting in hepatotoxicity; closely monitor patients for appearance of malaise,weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness

Oxcarbazepine (Trileptal)

Pharmacologic activity primarily from 10-monohydroxy metabolite (MHD) of oxcarbazepine.

May block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair

synaptic impulse propagation. Anticonvulsant effect may also occur by affecting potassiumconductance and high-voltage activated calcium channels. Drug pharmacokinetics similar in

children > 8 y and adults. Children

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Conversion to monotherapy: 600 mg/d PO divided bid initially; gradually reduce dose ofconcomitant anticonvulsants in about 3-6 wk and gradually increase oxcarbazepine dose in 2-4

wk; may increase oxcarbazepine dose prn by a maximum of 600 mg/d qwk; closely monitorpatients during transition phase for anticonvulsant adverse effects

Start of monotherapy: 600 mg/d PO divided bid initially; increase by 300 mg/d PO q3d to 1200mg/d; monitor patients for anticonvulsant adverse effects

Pediatric

1200 mg/d may increase phenytoin and phenobarbital serum concentrations significantly; can

reduce serum concentrations of oral contraceptives and make them ineffective; can increaseclearance of felodipine

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y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity

y Dosingy Interactionsy Contraindicationsy Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may

use if benefits outweigh risk to fetus

Precautions

Can cause cognitive adverse effects (eg, psychomotor slowing, impaired concentration, impaired

speech, impaired language); decrease initiation dose by 50% with renal impairment (CrCl

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Pediatric

12 years: Administer as in adults

y Dosingy Interactionsy Contraindicationsy Precautions

Thiazide diuretics increase toxicity of lithium, haloperidol, phenothiazines, neuromuscular

blockers, carbamazepine, fluoxetine, and ACE inhibitors

y Dosingy Interactionsy Contraindicationsy Precautions

Documented hypersensitivity; severe cardiovascular disease

y Dosingy Interactionsy Contraindicationsy Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Lithium toxicity (ie, diarrhea, vomiting, tremor, ataxia, drowsiness, muscle weakness) closely

related to serum levels and can occur at therapeutic doses; serum lithium determinations requiredto monitor therapy

Carbamazepine (Tegretol)

Indicated to treat epilepsy and trigeminal neuralgia. Research and clinical experience indicateeffectiveness in treating manic subtype schizoaffective disorder.

y Dosingy Interactionsy Contraindicationsy Precautions

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Adult

200-600 mg PO bid; 800-1200 mg/d maintenance

Pediatric

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y Expressed emotions must be reduced in all areas of a patient's life, including stress-reductiontechniques employed to prevent relapse and possible rehospitalization.

Prognosis

y The prognosis lies somewhere between that associated with schizophrenia and that associatedwith a mood disorder.

Patient Education

y Patients should be educated about the following:o Social skills trainingo Medication complianceo Reducing expressed emotionso Cognitive rehabilitationo Family therapy

y For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center.Also, see eMedicine's patient education article Schizophrenia.

y Family education should involve reduction of expressed emotions, criticism, hostility, or overprotection of the patient, which may led to decreases in relapse of this illness.

Miscellaneous

MedicolegalPitfalls

y Be familiar with local mental health laws.y If patients with schizoaffective disorder represent a danger to self or others or are gravely

disabled and are unwilling to seek help on a formal voluntary basis, they may need to be

committed for further evaluation and treatment.y If noncompliance with medications is an issue, one may seek a court order to force the patient

to take medications (eg, in lieu of rehospitalization), which may help increase medication

compliance.